Dr.Sidra Qaiser Learning Objectives  Students should be able to:  Define resting membrane potential and how it is generated.  Relate Nernst Equilibrium potential for sodium, potassium and chloride ion with resting membrane potential.  Describe the role of leak channels and sodium potassium pump in the generation of resting membrane potential.  Students should be able to:  Define action potential.  Describe the phases of action potential.  Explain the ionic basis of electrical events in an action potential and types of channels involved in it.  Describe the properties of action potential (all or none law, monophasic biphasic and compound potentials, electro tonic potential) and variation in action potential in different tissues like smooth, skeletal and cardiac muscles.  Illustrate difference between graded potential and action potential with the few examples (motor end plate potential, excitatory post synaptic potential, inhibitory post synaptic potential).  How action potential is propagated through mylinated and unmylinated nerve fibers.  What are the factors affecting the spread of conduction of action potential.  Animation What is the difference in ionic composition of ICF and ECF? What is potential difference? What is the charge on cell membrane? What is membrane potential?  The cell membranes of all body cells in the resting condition are, polarized which means that they show an electrical potential difference, commonly used term for potential difference is only potential.  Membrane potential refers to a separation of charges across the membrane or a difference in the relative number of cations and anions in the ICF and ECF. RESTING MEMBRANE POTENTIAL Basic Physics of Membrane Potentials  Diffusion potential  Equilibrium potwential Nernst Equation  Relation of diffusion potential to the concentration difference…… resulting in Nernst (equilibrium) potential  For any univalent ion at body temperature of 37° C  EMF (mV)= +/-61log (Conc.inside/Conc.outside)  Calculate for K+ and Na+  K= -61log(140/4)  Na= -61log(14/142)  Sign is –ve shows the polarity inside the cell. For potassium  If Ko = 5 mM and Ki = 140 mM EK = -61 log(140/4) EK = -61 log(35) EK = -94 mV For Sodium  If Nao = 142 mM and Nai = 14 mM EK = -61 log(14/142) EK = -61 log(0.1) EK = +61 mV Role of multiple ions Factors Affecting RMP  3 factors  Polarity of each ion  Membrane permeability of the ions  Concentrations of respective ions on both sides: (i= inside), (o= outside)  Vm= - 86 mV What is the role Na-K pump?  Electrogenic pump  Concentration gradient  Contributes -4mV. Action potential These are rapid transient changes in the membrane potential that spread rapidly along the nerve fiber membrane . Graded potentials Graded potentials Stages of Action potential  Afterdepolarisation: The descending limb of action potential dosenot reach to the baseline abbruptly, but it shows a delay of few seconds.  Decrease rate of K efflux.  Afterhyperpolarisation: The descending limb of action potential dips a little below the baseline of RMP.  Continued K efflux. Latent period  After a stimulus is applied to a nerve, there is a latent period before the start of the action potential. This interval corresponds to the time it takes the impulse to travel along the axon from the site of stimulation to the recording electrodes. Its duration is proportionate to the distance between the stimulating and recording electrodes and inversely proportionate to the speed of conduction. Propagation of Action potential Unmyelinated nerve fiber Myelination Myelinated nerve fiber Effects of myelination  Velocity  Energy  Sites Effect of electrolytes  Sodium:Decreasing the external Na+ concentration reduces the size of the action potential but has little effect on the resting membrane potential. The lack of much effect on the resting membrane potential would be predicted, since the permeability of the membrane to Na+ at rest is relatively low.  Potassium:Conversely, increasing the external K+ concentration decreases the resting membrane potential.  Calcium  Negative ions:Intracellular proteins Magnitude of stimulus  Sub threshold stimulus  Threshold stimulus  Suprathreshold stimulus Magnitude of stimulus  It is possible to determine the minimal intensity of stimulating current (threshold intensity) that, acting for a given duration, will just produce an action potential.  Action potential fails to occur if the stimulus is subthreshold in magnitude,produces graded potentials.  Suprathreshold stimuli produce action potential during relative refractory period. Refractory period "All-or-None" Law  The action potential fails to occur if the stimulus is subthreshold in magnitude, and it occurs with constant amplitude and form regardless of the strength of the stimulus if the stimulus is at or above threshold intensity. The action potential is therefore "all or none" in character and is said to obey the all-ornone law. Adaptation.  Slowly rising currents fail to fire the nerve because the nerve adapts to the applied stimulus, a process called adaptation.  Ionic basis: Monophasic action potential Biphasic action potential Compound Action potential Cardiac muscles  Plateau greatly prolongs the period of depolarization.  This type of action potential with plateau is seen in heart muscle fibers.  Opening of fast channels causes the spike portion of the action potential.  The slow, prolonged opening of the slow calcium- sodium channels mainly allows calcium ions to enter the fiber.  This is largely responsible for the plateau portion of the action potential. Smooth muscles  Sensitive to stretch  Slow wave potential  Spike potential s