Physiology as the science. Physiology as the science. Bioelectrical phenomena in Bioelectrical phenomena in

nerve cellsnerve cells

Defining of “physiology” Defining of “physiology” notionnotion

Physiology is the science Physiology is the science about the regularities of about the regularities of organisms‘ vital activity in organisms‘ vital activity in connection with the external connection with the external environment.environment.

Method of physiologyMethod of physiology a) a) Observation Observation This is the method in which the scientists don‘t mix This is the method in which the scientists don‘t mix

in course of vital processes. They only make use of in course of vital processes. They only make use of vision and description of all changes. On the base of vision and description of all changes. On the base of this changes they make conclusions.this changes they make conclusions.

b) b) ExperimentExperiment There are two kinds of experiments: There are two kinds of experiments: acute and acute and

chronic.chronic. Acute experiment was doing with the helps Acute experiment was doing with the helps of anesthesia. It may be accompanied by cut off the of anesthesia. It may be accompanied by cut off the nerves, introduction the different substances. The nerves, introduction the different substances. The chronic experiment was doing in vital animals, for chronic experiment was doing in vital animals, for example, after the acute experiment scientists can example, after the acute experiment scientists can used the observation.used the observation.

Method of physiologyMethod of physiology c) c) ExaminationExamination This is the method of examine the patient with different This is the method of examine the patient with different

diseases, for example, with using the different diseases, for example, with using the different apparatuses.apparatuses.

d) d) SimulationSimulation We can simulation different processes as a laboratory We can simulation different processes as a laboratory

simulation or realistic simulation, for example, apparatus simulation or realistic simulation, for example, apparatus of artificial kidney or apparatus of artificial circulation. It of artificial kidney or apparatus of artificial circulation. It may be the simulation the different processes by means may be the simulation the different processes by means of computers.of computers.

Measurement of the Measurement of the membranemembrane potentialpotential of of the nerve fiber usingthe nerve fiber using a microelectrodea microelectrode

Basic ConceptsForces that determine ionic movement

Electrostatic forcesOpposite charges attractIdentical charges repel

Concentration forcesDiffusion – movement of ions through

semipermeable membraneOsmosis – movement of water from region of

high concentration to low

BasicBasic mechanismsmechanisms of transport of transport

Gating of Gating of protein protein channelschannels provides a provides a means of means of controlling ion controlling ion permeability of permeability of thethe channels.channels.

I. Membrane Resting Potential

A constant potential difference across the resting cell membrane

Cell’s ability to fire an action potential is due to the cell’s ability to maintain the cellular resting potential at approximately –70 mV (-.07 volt)

The basic signaling properties of neurons are determined by changes in the resting potential

Concept of Resting Potential (RP)Concept of Resting Potential (RP) A potential difference across the cell A potential difference across the cell

membrane at the rest stage or when the membrane at the rest stage or when the cell is not stimulated.cell is not stimulated.

Property:Property: It is constant or stableIt is constant or stable It is negative inside relative to the outsideIt is negative inside relative to the outside Resting potentials are different in Resting potentials are different in

different cells.different cells.

Resting Membrane Potential

Na+ and Cl- are more concentrated outside the cell

K+ and organic anions (organic acids and proteins) are more concentrated inside.

Active TransportActive Transport

Movement of molecules and ions against Movement of molecules and ions against their concentration gradients.their concentration gradients.

– From lower to higher concentrations.From lower to higher concentrations. Requires ATP.Requires ATP. 2 Types of Active Transport:2 Types of Active Transport:

– PrimaryPrimary

– SecondarySecondary

Primary Active TransportPrimary Active Transport

ATP directly required ATP directly required for the function of the for the function of the carriers.carriers.

Molecule or ion binds Molecule or ion binds to carrier site.to carrier site.

Binding stimulates Binding stimulates phosphorylation phosphorylation (breakdown of ATP).(breakdown of ATP).

Conformational Conformational change moves change moves molecule to other molecule to other side of membrane.side of membrane.

P

Extracellular fluid1. Three sodium ions (Na+) and adenosine triphosphate (ATP) bind to the carrier protein.

2. The ATP breaks down to adenosine diphosphate (ADP) and a phosphate (P) and releases energy.3. The carrier protein changes shape, and the Na+ are transported across the membrane.

4. The Na+ diffuse away from the carrier protein.

5. Two potassium ions (K+) bind to the carrier protein.

6. The phosphate is released.

7. The carrier protein changes shape, transporting K+ across the membrane, and the K+ diffuse away from the carrier protein. The carrier protein can again bind to Na+ and ATP.

Cytoplasm Na+

ATP

K+

Breakdown of ATP(releases energy)

Carrier protein changesshape (requires energy) ADP

1

3

2

Carrier protein resumesoriginal shape

Na+

Na+ K+

P

K+

45

6

7

ATP binding site

Carrier protein

Intracellular vs extracellular ion concentrations

Ion Intracellular Extracellular

Na+ 5-15 mM 145 mMK+ 140 mM 5 mMMg2+ 0.5 mM 1-2 mMCa2+ 10-7 mM 1-2 mMH+ 10-7.2 M (pH 7.2) 10-7.4 M (pH 7.4)

Cl- 5-15 mM 110 mM

Resting Membrane Potential

Potassium ions, concentrated inside the cell tend to move outward down their concentration gradient through nongated potassium channels

But the relative excess of negative charge inside the membrane tend to push potassium ions out of the cell

Resting Membrane Potential

• But what about sodium?• Electrostatic and Chemical forces act together on

Na+ ions to drive them into the cell • The Na+ channel close during the resting state

Na+ is more concentrated outside than inside and therefore tends to flow into the cell down its concentration gradient

Na+ is driven into the cell by the electrical potential difference across the membrane.

Resting Potential

Postulated Postulated mechanismmechanism of the of the sodium-potassium pumpsodium-potassium pump

The formation of resting potential The formation of resting potential depends on:depends on:

Concentration difference of KConcentration difference of K++ across across the membranethe membrane

Permeability of NaPermeability of Na++ and K and K++ during the during the resting stateresting state

NaNa++-K-K++ pump pump

Factors that affect resting Factors that affect resting potentialpotential

Difference of KDifference of K++ ion concentration ion concentration across the membraneacross the membrane

Permeability of the membrane to NaPermeability of the membrane to Na++ and Kand K++..

Action of NaAction of Na++ pump pump

Basic Electrophysiological Basic Electrophysiological Terms I:Terms I:

PolarizationPolarization: a state in which membrane is : a state in which membrane is polarized at rest, negative inside and positive polarized at rest, negative inside and positive outside.outside.

DepolarizationDepolarization: the membrane potential : the membrane potential becomes less negative than the resting potential becomes less negative than the resting potential (close to zero). (close to zero).

HyperpolarizationHyperpolarization: the membrane potential is : the membrane potential is more negative than the resting level.more negative than the resting level.

Basic Electrophysiological Terms I:Basic Electrophysiological Terms I:

ReverspolarizationReverspolarization: a reversal of membrane : a reversal of membrane potential polarity. potential polarity.

The inside of a cell becomes positive relative to the The inside of a cell becomes positive relative to the outside.outside.

RepolarizationRepolarization: restoration of normal polarization : restoration of normal polarization state of membrane. state of membrane.

a process in which the membrane potential returns a process in which the membrane potential returns toward from depolarized level to the normal resting toward from depolarized level to the normal resting membrane value.membrane value.

Effect of stimuli of increasing Effect of stimuli of increasing voltages to elicit an voltages to elicit an actionaction potentialpotential

Typical action potentialTypical action potential

II Action Potential

Successive Stages:

(1) Resting Stage

(2) Depolarization stage

(3) Repolarization stage

(4) After-potential stage

(1)

(2) (3)

(4)

The Action PotentialThe Action Potential

Components/characteristicsComponents/characteristics

– RMPRMP

– Depolarizing stimulusDepolarizing stimulus

– ThresholdThreshold

– Rapid NaRapid Na++ entry entry (depolarization)(depolarization)

– IsopotentialIsopotential

– OvershootOvershoot

– Repolarization (KRepolarization (K++ moves out)moves out)

– Undershoot (after-Undershoot (after-hyperpolarization)hyperpolarization)

– Absolute refractory Absolute refractory periodperiod

– Relative refractory Relative refractory periodperiod

PropagationPropagation of of action action potentials in potentials in both directions both directions along a along a conductiveconductive fiberfiber

SaltatorySaltatory conductionconduction along a myelinated axon. along a myelinated axon. Flow of electricalFlow of electrical current from node to node is current from node to node is

illustrated by the arrows.illustrated by the arrows.