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Ch 4 Neuronal Physiology

Neuron structure The human brain contains around 85-100 billion neurons and 1 trillion neuroglial cells. The spinal cord contains around 100 million neurons. 1. multipolar neuron (most common type of neuron) is a nerve cell and consists of 3 basic

parts: cell body, dendrites, and axon 2. Dendritic zone = cell body and dendrites 3. dendrites (dendros – tree) are branched processes off the cell body (soma) a. some neurons have up to 1,000’s of dendrites b. part of neuron that is stimulated by other neurons c. receptive end of neuron, because contains receptors for neurotransmitters from other neurons

4. cell body (soma) a. location of nucleus b. axon hillock – part of cell body from which the axon arises (some include the very first

part of the axon as part of the axon hillock) c. axon hillock is the trigger zone where the first AP occurs that then self-propagates as a

nerve impulse d. axon hillock has a dense concentration of voltage-gated Na+ and K+ channels

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5. axon a. long and thin process that extends out from the dendrites and soma (cell body); 1. only one axon per neuron; conducts nerve impulse down it to the axon terminal 2. An axon can divide into many branches called telodendria (Greek–end of tree). At

the end of each telodendron is an axon terminal b. axon originates from the axon hillock of the cell body c. nerve impulse conducted down the axon to the axon terminal where it dies out d. plasma membrane –axolemma e. cytoplasm – axoplasm f. end of axon forms axon terminal g. myelin sheath – covering around the axons of most neurons 1. Function a. protect and insulate the axon b. increase the speed of nerve impulse conduction 1. unmyelinated – 5 mph 2. myelinated – 250 mph (100m/sec)(around 50x faster) 2. unmyelinated axon – does not contain myelin sheath 3. myelinated axon – contains myelin sheath a. 2 types of neuroglial cells make the myelin sheath (cells wrap around the axon

up to 200x) 1. oligodendrocytes - make myelin sheaths in CNS (brain and spinal cord) 2. Schwann cells (neurolemmocyte) in the PNS (peripheral nervous system –

everything outside the CNS); about 1 mm in length 3. the axons of most neurons are myelinated b. myelin sheath is discontinuous covering around axon c. nodes of Ranvier (myelin sheath gap)– gaps between the cells that form the

myelin sheath; the nodes are about 0.1 mm in width; occur on both CNS and PNS axons

h. telodendria 1. branches of an axon 2. each branch ends at an axon terminal 3. one axon of a neuron can synapse with 1000 or more other neurons

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Synapse (Gk. Syn – to join) 1. junction between 2 neurons (neuronal synapse) or between neuron and its effector or

target cell (neuromuscular junction or neuroglandular synapse) 2. Components a. axon terminal (axon ending) of presynaptic neuron b. synaptic vesicles in axon terminal filled with neurotransmitter c. synaptic cleft (20-30 nm, 1 millionth of an inch) – interstitial fluid filled gap between

axon ending and membrane of next cell d. postsynaptic membrane of effector cell

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Synaptic transmission at Neuron to Neuron Synapse (neuronal synapse) All of the events described only last for about 0.5 msec 1. presynaptic neuron synapses with the postsynaptic neuron 2. stimulate the dendritic zone of the presynaptic neuron 3. impulse travels down its axon to axon terminal 4. Ca2+ influx from IF into the axoplasm of the axon terminal a. nerve impulse opens voltage-gated calcium ion channels in axolemma of axon terminal b. Ca2+ active transport pumps in axolemma create diffusion gradient c. Ca2+ bind to synaptotagmin (protein) on synaptic vesicle d. The secretory vesicle then migrates to the axolemma where the calcium-bound

synaptotagmin binds to SNARE proteins in the axolemma to trigger exocytosis e. All Nt releases by exocytosis are Ca2+-dependent. 5. exocytosis of neurotransmitter-filled vesicles through the axolemma and into the synaptic

cleft (20-50 nm in width) 6. neurotransmitter diffuses across the cleft and binds to receptors (integral membrane

proteins) embedded in the plasma membrane on the next cell 7. neurotransmitter may stimulate or inhibit activity in the next cell 8. neurotransmitter effects only last for a few msec before they are broken down by enzymes

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Somatic Neuromuscular Junction (NMJ) – special type of synapse 1. junction where the axon terminal of a somatic motor neuron meets the motor end plate of

a muscle cell 2. Acetylcholine is the neurotransmitter released by exocytosis of the synaptic vesicles Ion Movements through Ion Channels and Electric Currents 1. Electric current, any movement of electric charge carriers, such as subatomic charged

particles (e.g., electrons having negative charge, protons having positive charge) or ions (atoms that have lost or gained one or more electrons),

2. Since ions are charged species, they can carry electrical current in solutions. When ions traverse the permeation pathway of an ion channel from one side of the membrane to the other side, their movement generates an ionic current that can be measured by using electrophysiological methods.

3. Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. With respect to the exterior of the cell, typical values of membrane potential, normally given in millivolts, range from –40 mV to –80 mV.

4. All animal cells are surrounded by a membrane composed of a lipid bilayer with proteins embedded in it. The membrane serves as both an insulator and a diffusion barrier to the movement of ions. Transmembrane proteins, also known as ion transporter or ion pump proteins (active transport pumps), actively push ions across the membrane and establish concentration gradients across the membrane, and ion channels allow ions to move across the membrane down those concentration gradients. Ion pumps and ion channels are electrically equivalent to a set of batteries and resistors inserted in the membrane, and therefore create a voltage between the two sides of the membrane.

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Differences in the concentrations of ions on opposite sides of a cellular membrane lead to a voltage called the membrane potential. Typical values of membrane potential are in the range –40 mV to –70 mV. Many ions have a concentration gradient across the membrane, including potassium (K+), which is at a high concentration inside and a low concentration outside the membrane. Sodium (Na+) and chloride (Cl−) ions are at high concentrations in the extracellular region, and low concentrations in the intracellular regions. These concentration gradients provide the potential energy to drive the formation of the membrane potential. This voltage is established when the membrane has permeability to one or more ions. In the simplest case, illustrated here, if the membrane is selectively permeable to potassium, these positively charged ions can diffuse down the concentration gradient to the outside of the cell, leaving behind uncompensated negative charges. This separation of charges is what causes the membrane potential. Note that the system as a whole is electro-neutral. The uncompensated positive charges outside the cell, and the uncompensated negative charges inside the cell, physically line up on the membrane surface and attract each other across the lipid bilayer. Thus, the membrane potential is physically located only in the immediate vicinity of the membrane. It is the separation of these charges across the membrane that is the basis of the membrane voltage.

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Nerve (or muscle) impulse 1. a series of self-propagating action potentials moving down the axolemma of a neuron’s

axon; self-propagate means that one event triggers the next (e.g., falling dominoes) 2. in the body, electrical currents reflect the flow of ions rather than free electrons. Currents

move down plasma membranes rather than through copper wires. 3. a nerve impulse involves the movement of ions (Na+, K+) across the axolemma 4. a muscle impulse is identical to a nerve impulse Ion Diffusion Channels in the Plasma Membrane – channels and gates constructed from

transmembrane proteins embedded in the membrane; ions can’t cross through phospholipid bilayer. Despite the small differences in their radii, ions rarely go through the "wrong" channel. For example, sodium or calcium ions rarely pass through a potassium channel. When a channel is open, ions permeate through the channel pore down the transmembrane concentration gradient for that particular ion.

1. Neurotransmitter (ligand) -gated ion channels (ligand is a molecule that binds to another) a. on dendrites and cell bodies at synapses; on

motor end plate at NMJ b. ion gates open in response to

neurotransmitter binding to receptor associated with channel’s gate

c. might be Na+, K+, or Cl- channels d. ions df thru channel when gate opens

2. Voltage-gated ion channels a. occur in the axon hillock of cell body and on

axolemma of the axon 1. gates to these channels open and close in

response to ion movements across the membrane that result in voltage changes

2. these channels are essential to the initiation and propagation of a nerve impulse

3. Action potentials only occur where there is a high concentration of voltage-regulated gated channels.

4. as a result, the first action potential that develops into a nerve impulse originates at the axon hillock and propagates down the axon

b. Na+ or K+ channels that open and close in response to voltage changes across membrane

c. these channels are responsible for the action potentials on the axon 3. Leak (passive) channels (Na+, K+, and Cl- ions) a. always open (not gated) b. Na+ and K+ diffuse through leak channels from one side of the membrane to another

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c. plasma membrane generally contains small diameter leakage channels d. Non-permeating anions (A-) are negatively-charged proteins inside the cell that cannot

df thru leak channels.

Trigger Zone of Neuron is at Axon Hillock where 1st AP occurs 1. The axon hillock is a specialized part of the cell body (or soma) of a neuron that connects to

the axon. 2. the first AP is generated at the trigger zone of the axon hillock. All-or-None 1. a nerve impulse is an all-or-none phenomenon 2. if the first AP occurs, then it will generate a nerve impulse 3. if the first AP does not occur, then the nerve impulse will not occur Na+/K+ ATPase Active Transport Antiport Pumps – found on every part of neuron (DZ, axon) 1. maintain the resting potential across the membrane by creating (ion diffusion gradients) an

unequal distribution of Na+ and K+ across the membrane in a resting cell. The diffusion gradients serve as the energy source to generate AP’s

2. essential for the ability of a cell to generate a nerve impulse 3. if the pumps stop operating then an irritable cell like a neuron can no longer generate

nerve impulses and organs like the brain would stop functioning. Ions eventually diffuse through leak channels and reach equilibrium on both sides of membrane

4. embedded within the plasma membrane of irritable cells like neurons and muscle cells 5. ATP-dependent 6. about 70% of ATP produced by neurons used to operate the pumps (typical neuron has

millions of pumps) 7. Na+/K+ exchanged by Antiport Pump across the plasma membrane a. Na+ pumped out of cell to IF b. K+ pumped into the cytoplasm

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8. the active transport pumps create ion diffusion gradients across the membrane that serve as sources of potential energy that can be converted to the kinetic energy of ion movements that generate an AP

Membrane Potential (voltage) 1. Differences in the concentrations of ions on opposite sides of a cellular membrane lead to a

voltage called the membrane potential. 2. form of stored energy like a battery 3. voltage across a biological membrane measures the magnitude of the concentration or df

gradients for ions across the membrane in mV 4. voltage is created by the separation of ions due to Na+/K+ AT pump Potentials Associated with a Nerve Impulse (AP, RP, TP) 1. Action Potentials (AP)

a. APs are a rapid change in membrane voltage as Na+ and K+ move across it b. action potentials are first generated at the trigger zone of the axon hillock of the soma

where the axon arises. AP’s are self-propagated as a nerve impulse on the axon c. APs require voltage-gated ion channels d. AP’s self-propagate as a nerve impulse that sweeps out from the axon hillock and then

down the axon; APs involve a brief (1-2 msec) reversal of membrane potential with a total amplitude of about 100 mV (from -70 mV to +30 mV)

e. events that lead to the first AP occur at synapses in the dendritic zone of a multipolar neuron (they occur at the motor end plate of a muscle cell)

f. AP’s generally occur as a result of Nt-R binding at a synapse in the dendritic zone or due to modality (e.g., pain, touch) that stimulates dendrites of sensory neurons

g. when action potentials occur, Na+ and K+ move across the membrane

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2. Resting Potential (RP = approx -70 mV)(state of relative negativity across the membrane) a. voltage that occurs across a membrane that is at rest or unstimulated (approx -70 mV) b. it is due to a separation of charged ions across the membrane (e.g., Na+ , K+, and anions

inside the cytoplasm) caused the the Na+/K+ AT pump c. Polarity: neuronal membranes have slightly more positive ions on the outside and

slightly more negative ions on the inside 1. Cytoplasmic Anions (A-) a. unable to penetrate the plasma membrane so give the cytoplasm a negative

charge relative to the ECF b. Anionic Proteins: most cytoplasmic anions are intracellular proteins that carry

a net negative charge. 2. Cytoplasmic anions that cannot escape because of their size and charge include

phosphates, sulphates, small organic acids, and proteins. 3. Proteins have both negatively and positively charged functional groups on their aa’s,

but more negative than positive so the net charge is usually negative 4. the inner surface of the cell is more negative than the outside due to negatively

charged intracellular proteins (A-) d. Measuring the Resting Potential 1. Magnitude of the charge separation equals about -70 mV. The charge separation is

a potential (voltage) that is measured in millivolts (mV) 2. Sign on the charge refers to conditions on the cytoplasmic side of the membrane. a. A negative sign means that the inside or cytoplasm is more negative (or less

positive) than the outside of the plasma membrane. b. A positive sign means that the inside is more positive (or less negative) then the

outside of the membrane. c. The sign on the potential is always with respect to the interior of the cell 3. Polarized membrane: charge separation creates + and – poles on opposite sides of

the membrane

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3. Threshold Potential (TP = -55 mV) a. potential or voltage that must be reached before AP will occur b. Voltage across the membrane at which the voltage-gated Na+ channels at the trigger

zone on the axon hillock and the axon open wide and Na+ diffuses into the cytoplasm c. at TP the axolemma undergoes a 1000-fold increase in sodium ion permeability d. TP is often around -55 mV. Depolarization and Repolarization (voltage changes that are relative to RP) Two terms that describe events that occur during an AP as Na+ move into cell and K+ move out 1. Depolarization (Na+ influx; potential becomes less neg or more pos) a. an event that causes a decrease in membrane potential away from RP (-70 mV)

towards 0 mV and beyond to +30 b. Na+ influx causes the inside of the cell to become less negative (or more positive) than

RP (or closer to 0 mV) -70 to -50 to 0 (reverse polarity if goes to +30)

c. depolarization also refers to the reverse polarity that occurs during an AP d. due to Na+ current fluxing into the cell (Na+ influx) and causing graded potentials (local

changes in membrane potential) 1. the influx of the positively charged sodium ions adds positive charge to the inside of

the cell as the inside becomes less and less negative 2. as sodium ions move into the cytoplasm they subtract positive charge from the

outside of the membrane as it is added to the inside 2. Repolarization (K+ efflux; potential becomes more neg or less pos) a. K+ efflux event that restores the RP across the membrane as a result of K+ moving out of

the axon through ion channels and into the interstitial fluid (during repolarization the polarity across the membrane may go from a +30mV to -70mV)

+30 -> +10 -> 0 -> -15 -> -55 -> -70 b. repolarization causes the axoplasm to become more negative (or less positive) c. the efflux of positively charged potassium ions causes the inside of the cell to become

less positive (more negative) as the outside of the cell becomes more positive 3. Hyperpolarization - an event that causes an increase in the potential (more neg than RP)

across the membrane (-70mV to -80mV) Graded (local) Potentials 1. ion movements through ion channels create local and temporary changes in membrane

potential (i.e., graded potentials). a. Large or small changes in the membrane potential as ions move across membrane

through channels. b. Graded potentials occur at the synapse and at the MEP of NMJ c. graded potentials occur when ions move through membrane channels (Na+ in or K+ out

will generate a localized change in the potential) d. synapses on dendrites and cell bodies generate graded potentials 2. for example, if membrane potential changes from -70 to -60 mV, then that would

represent a graded potential depolarization of 10 mV

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3. a change of -10 to -35 mV would be a graded potential repolarization of 25 mV 4. They are not the same as AP’s. 5. Graded potentials become AP’s once TP is reached Nerve Impulse is a Series of Self-Propagating Action Potentials 1. Each AP lasts for about 1 msec 2. neurotransmitter-receptor binding at the synapse triggers ion fluxes across the membrane

that results in the summation of EPSP’s and IPSP’s at the axon hillock 3. dense concentrations of voltage-gated ion channels are only found on the trigger zone of

the axon hillock and on the axon, hence AP’s originate at the axon hillock and are propagated along the axon to the axonal endings

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Note: During an action potential, very few of the total number of ions move across the membrane. In reality, only about one ion in a million crosses the membrane to produce an action potential. Even after thousands of action potentials, the cytosol has a higher [K+] and a lower [Na+]

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Events associated with the first AP on the axon hillock that generates nerve impulse on axon 1. Excitatory Neurotransmitter-Receptor Binding at Synapse a. When the impulse arrives at the axon terminal of the presynaptic neuron, it triggers a

Ca2+ influx that leads to the exocytosis of neurotransmitter into the synaptic cleft b. the neurotransmitter diffuses across the cleft and binds to a receptor on the

postsynaptic membrane that is physically attached to the gates of ion channels c. at an excitatory synapse the neurotransmitter-receptor binding opens the gates of Na+

channels d. as the Na+ channel gates open, Na+ diffuse through the channels and into the cell to

create a graded or local potential that spreads to the axon hillock e. Since Na+ carry a positive charge, this inward flux of Na+ into the cell makes the interior

of the cell more positive as the outside becomes less positive (or more negative) 2. Na+ enter and diffuse1 to the axon hillock region of the cell body and raise its positivity to

TP (EPSP); this is called summation which triggers the first AP at the trigger zone of the axon hillock just before the start of the axon. Once initiated, action potentials self-propagate down the axon as a nerve impulse. Na+ repel like charges. Hence, Na+ influx jostles Na+ towards axon hillock.

3. Depolarization a.. if sufficient Na+ accumulate in the axon hillock, then the positivity of the interior of the

cell at the axon hillock reaches threshold potential (usually around -55 mV) b. All-or-None: once threshold potential is reached, the voltage-sensitive Na+ gates open

and Na+ diffuse inward to depolarize the membrane and the first action potential occurs at the axon hillock of the cell body

c. once the first AP occurs, it self-propagates as a series of APs down the axon d. the membrane depolarizes and generally a reverse polarity is observed e. at the height of the AP, the Na+ gates close and the K+ gates open 4. Repolarization a. K+ diffuse from the inside of the cell to the outside carrying their positive charge with

them b. the K+ efflux causes the repolarization of the membrane. Repolarization restores the

resting membrane potential of -70 mV. c. K+ gates close at the end of repolarization d. repolarization restores the internal negativity of the cytoplasm and leads to the resting

potential 5. Each AP involves the movement of Na+ and K+ by diffusion through ion channels a. depolarization due to Na+ influx b. repolarization due to K+ efflux (K+ move out of cell) 6. the diffusion gradients for Na+ and K+ are generated and maintained by the ATP-dependent

activity of the Na+/K+ active transport pump

1 Actually, once inside the neuroplasm, the positively-charged sodium ions “nudge” adjacent ions down the axon by electrostatic

repulsion and attract negative ions away from the adjacent membrane. As a result, a wave of positivity moves down the axon without any individual ion moving very far. Once the adjacent patch of membrane is depolarized, the voltage-gated sodium ion channels in that patch open, regenerating the cycle. The process repeats itself down the length of the axon, with an action potential generated at each segment of the membrane

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Self-propagating AP’s 1. the first AP triggers all of the others to create a nerve impulse a. a nerve impulse has been likened to the way in which dominos fall (tip the first one and

all of the others fall in sequential fashion) b. another analogy is with the way in which a fuse burns (light the fuse and it burns from

one end to the other) 2. when threshold potential occurs at one section of the membrane, the Na+ move into the

cell and diffuse laterally towards the next segment of the axon. The Na+ diffusing in cause that section of the axon to reach TP

3. once TP is reached at an adjacent section of the membrane, it generates an AP

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Saltatory Conduction. The impulse “jumps” from node to node in a myelinated fiber

Saltatory Conduction (L. saltere – “to hop or leap or jump”) 1. myelination increases the speed of nerve impulse conduction a. unmyelinated fiber – 5 mph (2m/sec)(continuous conduction) b. myelinated fiber – 250 mph (100m/sec)(saltatory conduction) – few AP’s since they only

occur at the nodes 2. Schwann cells (neurolemmocytes in the PNS) and oligodendrocytes (CNS) myelinate axons

with a myelin sheath. These are glial cells that wrap themselves tightly around the axon in concentric rings

3. the myelin sheath is discontinuous with gaps called Nodes of Ranvier (myelin sheath gaps) a. nodes about 1 mm apart (length of Schwann cells); the node itself is about 0.1mm wide. b. there are no ion channels under myelin sheath c. the voltage-gated Na+ and K+ channels and the Na+/K+ pumps are concentrated at the

nodes d, in contrast, an unmyelinated axon has channels and active transport pumps along the

entire axolemma of the axon e. AP’s only occur at the nodes of Ranvier (local current flow)

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4. Mechanism of Saltatory Conduction (L. saltere – to leap or jump) a. Na+ influx diffuses under myelin to next node which raises membrane potential to TP b. once TP reached, AP’s triggered at the next node that self-propagate along the node to

the next myelin covered portion of axolemma c. the impulse seems to jump from one node to the next d. Na+ df under Schwann cell is around 50x faster than a series of continuous APs on an

unmyelinated axon 5. Saltatory conduction is faster than conduction on an unmyelinated fiber because a. far fewer AP’s b. the rate that Na+ diffuse under the myelin is 50x faster than the time it would take AP’s

to travel the same distance 6. nodes have 2000-12000 voltage-gated Na+ channels per um2 Local anesthetics (the ‘caines) 1. lidocaine, procaine, novacaine are used when one sutures a gash or during dental work 2. these drugs work by blocking the opening of voltage-gated Na+ channels on the axon and

prevent the nerve impulse from spreading by the blocked region 3. Local anesthetic agents prevent transmission of nerve impulses w/o causing

unconsciousness. 4. Each of the local anesthetics have the suffix "-caine" in their names. 5. Local anesthetics include procaine, amethocaine, cocaine, benzocaine, tetracaine, lidocaine,

prilocaine, bupivicaine, levobupivacaine, ropivacaine, mepivacaine, dibucaine) Excitatory and Inhibitory Neurotransmitters Some neurotransmitters excite the postsynaptic neuron while others inhibit it 1. excitatory neurotransmitters make it more likely that the postsynaptic neuron will be

stimulated to generate a nerve impulse a. bind to receptors and open Na+ channels and depolarize the postsynaptic neuron b. both Na and K+ will move through these ion channels in opposite directions c. the channels allow far more Na+ to pass through than K+ so the effect of opening the

channels is to allow a relatively large number of Na+ to enter the cell and depolarize the membrane towards TP so that an impulse occurs

d. glutamate is the most common excitatory Nt in the brain e. excitatory Nt trigger EPSP’s on the postsynaptic membrane. EPSP – excitatory

postsynaptic potential 2. inhibitory neurotransmitters make it less likely that the postsynaptic neuron will be

stimulated to generate a nerve impulse a. bind to receptors and open K+ (or Cl-) channels that hyperpolarizes the membrane, thus

making it less likely that an impulse will occur b. GABA (gamma-aminobutyric acid) is the most common inhibitory neurotransmitter in

the brain c. inhibitory Nt trigger IPSP’s on the postsynaptic membrane. IPSP – inhibitory

postsynaptic potential

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Chemicals that Affect the NMJ 1. Venom of black widow spider a. stimulates release of ACh from secretory vesicles at all cholinergic synapses to include

somatic motor neurons into cleft at NMJ. This causes prolonged depolarization at cholinergic synapses. Cholinergic synapses are ones in which the presynaptic neuron release ACh

b. the most harmful effect is tetany of the diaphragm that leads to respiratory paralysis and suffocation (can’t breathe)

c. black widow spider can kill small prey (not humans) d. black widow spiders eat mostly insects (which don’t have diaphragms). 1. The venom paralyzes the muscle of insect prey 2. spider bites prey after it dies and then injects digestive enzymes into its body to

liquefy internal organs, then sucks the liquid out of the body and into its mouth This spider's bite is much feared because its venom is reported to be 15 times stronger

than a rattlesnake's. In humans, bites produce muscle aches, nausea, and a paralysis of the diaphragm that can make breathing difficult; however, contrary to popular belief, most people who are bitten suffer no serious damage—let alone death. But bites can be fatal—usually to small children, the elderly, or the infirm. Fortunately, fatalities are fairly rare; the spiders are nonaggressive and bite only in self-defense, such as when someone accidentally sits on them.

2. Curare a. extracted from bark of tropical plants that grow in South America (e.g., Strychnos

toxifera) b. initially used by indigenous Amazonian Indians of SA to tip arrowheads or blowgun darts

for hunting c. curare binds to ACh receptors on the MEP of NMJ without opening up ion channels d. curare prevents ACh from binding to ACh receptors making it impossible to stimulate

skeletal muscle cells. Causes weakness of skeletal muscle that leads to paralysis. Death by asphyxiation since diaphragm is skeletal muscle. Curare effects occur within 5 minutes.

e. this results in paralysis of skeletal muscle cells to include the diaphragm f. curare leads to respiratory paralysis and death by suffocation Curare is active — toxic or muscle-relaxing, depending on the intended use — only by an

injection or a direct wound contamination by poisoned dart or arrow. It is harmless if taken orally because curare compounds are too large and highly charged to pass through the lining of the digestive tract to be absorbed into the blood. For this reason, native tribes are able to eat curare-poisoned prey safely. Curare has no effect on taste.

3. Toxic alkaloids from skin of golden dart frog (golden poison frog) a. frog lives on Pacific coast of Columbia in rain forests b. the frog is not venomous. It is poisonous. It may be the most poisonous of any living

animal c. the poison is a self-defense mechanism that is stored in skin glands d. the frog’s are aposematically colored – very bright colors and patterns e the frogs taste terrible and the poison can kill prey

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f. as a result, prey do not bother the easy to spot and highly colorful frogs g. the poison is incredibly lethal. The golden dart frog is probably the only animal immune

to it The average dose carried will vary between locations, and consequent local diet, but the

average wild P. terribilis is generally estimated to contain about one milligram of poison, enough to kill about 10,000 mice. This estimate will vary in turn, but most agree this dose is enough to kill between 10 and 20 humans, which correlates to up to two African bull elephants.This is roughly 15,000 humans per gram.

h. the neurotoxic alkaloid in the skin of the golden dart frogs is called batrachotoxin (Gk. Batracho – frog)

1. 100 ug of batrachotoxin can kill a human being. That is the weight of 2 grains of table salt.

2. batrachotoxin is 15x more potent than curare 3. batrachotoxin binds to and irreversibly increases the permeability of Na+ channels

which leads to prolonged depolarization of muscle cells – this causes muscle tetany. a. Voltage-sensitive Na+ channels stay open all of the time

b. the poison kills by permanently blocking the ability to conduct nerve or muscle impulses; the neuron can’t fire, thus can’t transmit nerve impulses to effector cells like skeletal muscle cells

c. it will interfere with heart conduction which leads to cardiac arrest (fibrillation) and interfere with the diaphragm leading to suffocation

d. there is no antidote, but there are drugs that can reverse its effects i. The "poison dart" (or "poison arrow") frog does not produce batrachotoxin itself. It is

believed that the frogs get the poison from eating beetles or other insects in their native habitat. Frogs raised in captivity do not produce batrachotoxin, and thus may be handled without the risk of death.