Cell PhysiologyCell PhysiologyCell Membranes, Transport Across Cell Cell Membranes, Transport Across Cell

Membranes, Osmosis, Membrane PotentialsMembranes, Osmosis, Membrane PotentialsLectured by Bien Nillos, MDLectured by Bien Nillos, MD

The Cell MembraneThe Cell Membrane

Lipid BilayerLipid Bilayer

Phospholipids – hydrophilic heads Phospholipids – hydrophilic heads and two fatty acid tails and two fatty acid tails (hydrophobic). Hydrophobic tails face (hydrophobic). Hydrophobic tails face each other and form a bilayer.each other and form a bilayer.

Lipid-soluble substances – cross cell Lipid-soluble substances – cross cell membranesmembranes

Water-soluble substances – cannot Water-soluble substances – cannot dissolve in the lipid membrane. dissolve in the lipid membrane.

ProteinsProteins

Integral Proteins – span the entire Integral Proteins – span the entire membrane, include ion channels and membrane, include ion channels and transport proteins.transport proteins.

Peripheral Proteins – located on Peripheral Proteins – located on either the intracellular or either the intracellular or extracellular side of the cell, include extracellular side of the cell, include hormone receptors.hormone receptors.

Intercellular ConnectionsIntercellular Connections

Tight junctions – zonula occludens, Tight junctions – zonula occludens, attachments between cells; may be attachments between cells; may be an intercellular pathway for solutes an intercellular pathway for solutes (impermeable vs. permeable)(impermeable vs. permeable)

Gap Junctions – attachments Gap Junctions – attachments between cells that permit between cells that permit intercellular communication.intercellular communication.

Transport Across MembranesTransport Across Membranes

DOES NOT REQUIRE ENERGYDOES NOT REQUIRE ENERGY•Simple Diffusion – “downhill”Simple Diffusion – “downhill”

PermeabilityPermeability – the ease with – the ease with which a solute diffuses through a which a solute diffuses through a membranemembrane

Factors that increase Factors that increase permeability – inc. oil/water permeability – inc. oil/water partition coefficient, dec. radius partition coefficient, dec. radius of the solute, dec. membrane of the solute, dec. membrane thicknessthickness

Let’s Imagine This…..Let’s Imagine This…..

Let’s Imagine This…..Let’s Imagine This…..

DOES NOT REQUIRE ENERGY:DOES NOT REQUIRE ENERGY:• Facilitated Diffusion: “Downhill”Facilitated Diffusion: “Downhill”

More rapid than simple diffusionMore rapid than simple diffusion Exhibits:Exhibits:

•StereospecificityStereospecificity•SaturationSaturation•CompetitionCompetition

REQUIRES ENERGY:REQUIRES ENERGY:• Primary Active TransportPrimary Active Transport: “Uphill”: “Uphill”

Requires direct input of metabolic Requires direct input of metabolic energy in the form of ATPenergy in the form of ATP

Is carrier-mediated.Is carrier-mediated. Examples: Na-K-ATPase Pump, Ca-Examples: Na-K-ATPase Pump, Ca-

ATPase pump, H-K-ATPase pump ATPase pump, H-K-ATPase pump (proton pump).(proton pump).

Let’s Imagine This…..Let’s Imagine This…..

REQUIRES ENERGY:REQUIRES ENERGY:• Secondary Active TransportSecondary Active Transport: “Uphill”: “Uphill”

Transport of two or more solutes is Transport of two or more solutes is coupledcoupled

• One of the solute (usually Na) is One of the solute (usually Na) is transported downhill and provides transported downhill and provides energy for the “uphill” transport of energy for the “uphill” transport of the other solute.the other solute.

OsmosisOsmosis

Osmolarity – concentration of Osmolarity – concentration of osmotically active particles in a osmotically active particles in a solutionsolution

Can be calculated using the following Can be calculated using the following equation:equation:• Osmolarity = g x COsmolarity = g x C• Where g – number of particles in a Where g – number of particles in a

solutionsolution• C – concentration (mol/L)C – concentration (mol/L)

Osmosis – the flow of water across a Osmosis – the flow of water across a semipermeable membrane from a semipermeable membrane from a solution with low solute solution with low solute concentration to a solution with high concentration to a solution with high solute concentration.solute concentration.

Osmotic pressure increases when the Osmotic pressure increases when the solute concentration increases.solute concentration increases.

Isotonic – two solutions having the Isotonic – two solutions having the same effective osmotic pressuresame effective osmotic pressure

Hypertonic – the solution with higher Hypertonic – the solution with higher effective osmotic pressureeffective osmotic pressure

Hypotonic – the solution with the Hypotonic – the solution with the lower effective osmotic pressurelower effective osmotic pressure

* Water flows from the hypotonic to the hypertonic * Water flows from the hypotonic to the hypertonic solutionsolution

Reflection coefficient – describes the Reflection coefficient – describes the ease with which a solute permeates ease with which a solute permeates a membrane (value = 0 to 1)a membrane (value = 0 to 1)• if 1 = solute is impermeable, creates an if 1 = solute is impermeable, creates an

osmotic pressure, causes water flow.osmotic pressure, causes water flow.• If 0 = solute is completely permeable, If 0 = solute is completely permeable,

will not exert any osmotic effect.will not exert any osmotic effect.

Diffusion Potential, Resting Membrane Diffusion Potential, Resting Membrane Potential and Action PotentialPotential and Action Potential

Ion channels – integral proteins that Ion channels – integral proteins that span the membrane and when open, span the membrane and when open, permit the passage of certain ions.permit the passage of certain ions.• Are selective Are selective • May be open or closedMay be open or closed• Conductance depends on the probability Conductance depends on the probability

that the channel is open; the higher the that the channel is open; the higher the probability that a channel is open, the probability that a channel is open, the higher the conductance or permeability.higher the conductance or permeability.

Voltage-gated channels – are opened Voltage-gated channels – are opened or closed by changes in membrane or closed by changes in membrane potential potential

Ligand-gated channels – opened or Ligand-gated channels – opened or closed by hormones, second closed by hormones, second messengers or neurotransmitters.messengers or neurotransmitters.

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Diffusion potential – potential Diffusion potential – potential difference generated across a difference generated across a membrane because of a membrane because of a concentration difference of an ion. concentration difference of an ion. • Diffusion potential can be generated Diffusion potential can be generated

only if the membrane is permeable to only if the membrane is permeable to the ion.the ion.

• The size of the diffusion potential The size of the diffusion potential depends on the size of the concentration depends on the size of the concentration gradient.gradient.

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The equilibrium potential is the The equilibrium potential is the diffusion potential that exactly diffusion potential that exactly balances the tendency for diffusion balances the tendency for diffusion caused by a concentration caused by a concentration difference.difference.

At electrochemical equilibrium, the At electrochemical equilibrium, the chemical and electrical driving forces chemical and electrical driving forces that act on an ion are equal and that act on an ion are equal and opposite, and no more diffusion of opposite, and no more diffusion of the ion occurs.the ion occurs.

Approximate values for Equilibrium Approximate values for Equilibrium potentials in Nerve and Musclepotentials in Nerve and Muscle

EENaNa = +65 mV = +65 mV EECaCa

22 = +120 mV = +120 mV EEKK = -85 mV = -85 mV EEClCl = -85 mV = -85 mV

Resting membrane potential – Resting membrane potential – expressed as the measured potential expressed as the measured potential difference across the cell membrane difference across the cell membrane in millivolts.in millivolts.

By convention, it is expressed as the By convention, it is expressed as the intracellular potential relative to the intracellular potential relative to the extracellular potential.extracellular potential.

Each permeable ion attempts to Each permeable ion attempts to drive the membrane potential toward drive the membrane potential toward its equilibrium potential. its equilibrium potential.

For example: the resting membrane For example: the resting membrane potential of nerve is -70 mV which is potential of nerve is -70 mV which is close to the calculated Kclose to the calculated K++ equilibrium equilibrium of -85 mV, but far from the of -85 mV, but far from the calculated Nacalculated Na++ equilibrium potential equilibrium potential (+65 mV); thus, at rest, the nerve (+65 mV); thus, at rest, the nerve membrane is far more permeable to membrane is far more permeable to K than Na.K than Na.

Depolarization – makes the Depolarization – makes the membrane potential less negative membrane potential less negative (the cell interior becomes less (the cell interior becomes less negative)negative)

Hyperpolarization – makes the Hyperpolarization – makes the membrane potential more negativemembrane potential more negative

Inward current – the flow of positive Inward current – the flow of positive charge into the cell.charge into the cell.

Outward current – flow of the positive Outward current – flow of the positive charge out of the cell. charge out of the cell.

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Action potential – property of Action potential – property of excitable cells that consists of a rapid excitable cells that consists of a rapid depolarization or upstroke, followed depolarization or upstroke, followed by repolarization of the membrane by repolarization of the membrane potential.potential.

Action potentials have stereotypical Action potentials have stereotypical size and shape, are propagating and size and shape, are propagating and are all-or-none. are all-or-none.

Threshold – the membrane potential Threshold – the membrane potential at which the action potential is at which the action potential is inevitable. Inward current inevitable. Inward current depolarizes the membrane. If the depolarizes the membrane. If the inward current depolarizes the inward current depolarizes the membrane to threshold, it produces membrane to threshold, it produces an action potential.an action potential.

Resting membrane potential – is Resting membrane potential – is approx. -70 mV, cell negative; the approx. -70 mV, cell negative; the result of the high resting result of the high resting conductance to Kconductance to K++ which drives the which drives the membrane potential toward the Kmembrane potential toward the K++ equilibrium potential.equilibrium potential.

Note: at rest, the NaNote: at rest, the Na++ channels are channels are closed and Naclosed and Na++ conductance is low. conductance is low.

Upstroke – inward current Upstroke – inward current depolarizes the membrane potential depolarizes the membrane potential to threshold.to threshold.

Depolarization causes Depolarization causes rapid opening rapid opening of the activation gatesof the activation gates of the Na of the Na++ channel, and the Nachannel, and the Na++ conductance of conductance of the membrane promptly increases.the membrane promptly increases.

Depolarization also closes the Depolarization also closes the inactivation gates of the Nainactivation gates of the Na++ channel. channel.

Depolarization slowly opens KDepolarization slowly opens K++ channels and increases Kchannels and increases K++ conductance to even higher levels conductance to even higher levels than at rest.than at rest.

RepolarizationRepolarization is caused by an is caused by an outward Koutward K++ current. current.

Absolute Refractory PeriodAbsolute Refractory Period – period – period during which another action potential during which another action potential cannot be elicited no matter how cannot be elicited no matter how large the stimulus.large the stimulus.

Relatively refractory periodRelatively refractory period – an – an action potential can be elicted during action potential can be elicted during this period only if a larger than usual this period only if a larger than usual inward current is provided.inward current is provided.

Absolute Refractory Period

Relative Refractory Period

-70 mV

-85 mV

Time in seconds

Resting Membrane Potential

AccommodationAccommodation – occurs when the cell – occurs when the cell membrane is held at a depolarized membrane is held at a depolarized level such that the threshold potential level such that the threshold potential is passed without firing an action is passed without firing an action potential potential (e.g. (e.g. hyperkalemiahyperkalemia in skeletal in skeletal muscles)muscles)

Propagation of Action PotentialsPropagation of Action Potentials – – occurs by the spread of local occurs by the spread of local currents to adjacent areas of currents to adjacent areas of membrane which are then membrane which are then depolarized to threshold and depolarized to threshold and generate action potentials.generate action potentials.

Conduction velocity is increased by:Conduction velocity is increased by:• Increase in fiber sizeIncrease in fiber size – increasing the – increasing the

diameter of a nerve fiber results in diameter of a nerve fiber results in decreased internal resistance.decreased internal resistance.

• MyelinationMyelination – myelin acts as an insulator – myelin acts as an insulator around nerve axons and increases around nerve axons and increases conduction velocity (conduction velocity (saltatory saltatory conductionconduction))

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SOLUTION 1 SOLUTION 2