The electrical properties of the plasma membrane (L3) 430-432

Ion Channels Ion channels are transmembrane proteins that transport inorganic ions in or out of the cell They transport ions down concentration gradient (require no energy) and 1000 times faster than carriers Ion channels have two important properties: Selectivity: allowing some ions to pass but not others K+ channels Na+ channels Ca2+ channels Cl- channels Gating : ion channels open and close in response to specific stimuli some channels inactivate before they close (open, inactivated, close) Movement of ions through ion channels constitute electrical current I (current) = V (voltage) / R(resistance) This is Ohms law

Copyright 2009 John Wiley & Sons, Inc. Gating of Ion Channels The gating (opening and closing) of ion channels occurs in response to a specific stimulus: Leakage (non-gated,) channels are always open nerve cells have more K+ than Na+ leakage channels as a result, membrane permeability to K+ is higher explains resting membrane potential of -70mV in nerve tissue Ligand-gated channels open and close in response to : - extracellular mediator (excitatory and inhibitory neurotransmitters). - intracellular mediators (Ca2+, ATP) Voltage-gated channels respond to a direct change in the membrane potential (voltage). There are Na+, K+ and Ca2+ voltage gated channels. Responsible for generation of action potential Mechanically gated ion channels respond to mechanical vibration or pressure. Copyright 2009 John Wiley & Sons, Inc.

Copyright 2009 John Wiley & Sons, Inc. Gating of Ion channels Copyright 2009 John Wiley & Sons, Inc.

ATP sensitive potassium channel causes Insulin secretion ATP…… closure of KATP channels Depolarization Opening of Ca2+ channels Release of insulin of exocytosis Compounds that close KATP channels cause insulin secretion

Copyright 2009 John Wiley & Sons, Inc. Graded potentials in response to opening mechanically-gated channels or ligand-gated channels Copyright 2009 John Wiley & Sons, Inc.

Ionic composition of the ICF and ECF ECF ICF Na+ 150 mM > 15 mM Na+ K+ 5 mM < 150 mM K+ Cl- 118 mM > 10 mM Cl- A- 10 meq/L < 132 meq/L A- Ca2+ 1.5 mM > 0.1 µM Ca2+ Mg2+ 1.0 mM 1.0 mM Mg2+ HCO3- 24 mM > 10 mM HCO3- pH 7.4 > pH 7.0 A- ARE IMPERMEABLE ANIONS

Membrane electrical charges

MEMBRANE POTENTIAL Extra cell Intra cell [K+] = 5mM [K+] = 150mM + - There is a tendency for K+ to leave the cell because of the concentration gradient. The loss of a cation leaves behind a small residual -ve charge. There is thus a tendency for K+ to enter the cell

Equilibrium Potential Extra cell Intra cell [K+] = 5mM [K+] = 150mM + - Diffusion Electro- static At equilibrium the diffusive forces will equal the electro-static forces so that there is no net movement of K+. This is termed an Equilibrium Potential. The diffusion force E = RT/zF [K+]e [K+]i The Nernst equation R is the Gas Constant - 8.314 J.K-1.mol-1 T is the absolute temperature = 273 + °C z is the ionic valency - for K+ = 1 F is the Faraday Constant = 96 480 C.mol-1

Because the log of 1/30 + -1.477 Ek = 61(-1.477) = - 90 mV [K+]e Ek = 61 log [K+]e [K+]i Ek = 61 log [5 mM]e [150 mMK+]i Ek = 61 log [1]e [30]i Ek = 61 log 1 30 Because the log of 1/30 + -1.477 Ek = 61(-1.477) = - 90 mV

GRAPHICAL REPRESENTATION OF THE NERNST EQUATION The relationship between the extracellular [K] and membrane potential, Em, is very non-linear. In particular small changes of [K] around the normal level have large effects on Em.

Equilibrium Potential Membrane Potential when electrical and chemical forces are balanced therefore there is no net movement of an ion Nearnst equation: Ek = 61 log [K+] outside / [K+] inside = 61 log 5 mM/ 150 mM = -90mV (Equilibrium potential for K+) ENa = 61 log [Na+] outside/ [Na+] inside = 61 log 150 / 15 = + 60 mV (Equilibrium potential for Na+)

Resting Membrane Potential (RMP) If K+ moves alone RMP = -90 mV If Na+ moves alone RMP = +60 mV RMP is closer to EK because the membrane at rest is more permeable to K+

Resting membrane potential

Resting Membrane Potential There is an electrical voltage difference between inside and outside of the cell membrane. There is of small build up of –ve charges at the cytosol side of the membrane Separation of –ve and +ve charges is measured in Volts (mV) and is called membrane potential.

Factors that contribute to resting membrane potential Unequal distribution of ions in the ECF and cytosol. Inability of most anions to leave the cell Na-K pump (electrogenic pump)

Resting Membrane Potential Negative ions along inside of cell membrane & positive ions along outside potential energy difference at rest is -70 mV cell is “polarized” Resting potential exists because concentration of ions are different inside & outside extracellular fluid rich in Na+ and Cl cytosol full of K+, organic phosphate & amino acids membrane permeability differs for Na+ and K+ 50-100 greater permeability for K+ inward flow of Na+ can’t keep up with outward flow of K+ Na+/K+ pump removes Na+ as fast as it leaks in

Membrane Potential Depolarization Cell is depolarized (-50mV) RMP (-70mV) Cell is polarized Cell is hyperpolarized Hyperpolarization (-90mV)

Membrane Potential Depolarization Cell is depolarized (-50mV) Na+ ions move into the cell (influx) RMP (-70mV) Cell is polarized K+ ions move out the cell (efflux) Cl- ions move into the cell (influx) Cell is hyperpolarized Hyperpolarization (-90mV) In many cases depolarization occurs if K+ is prevented to move outside the cell

Changes in membrane potentials Graded potentials

Stimulus strength and graded potentials

Graded Potentials Inhibitory Post Synaptic Potential Small deviations from resting potential of -70mV hyperpolarization = membrane has become more negative Excitatory Post Synaptic Potential depolarization = membrane has become more positive The signals are graded, meaning they vary in amplitude (size), depending on the strength of the stimulus and localized. Graded potentials occur most often in the dendrites and cell body of a neuron.

Electrical signals in neurons Neurons are electrically excitable due to the voltage difference across their membrane Communicate with 2 types of electric signals action potentials that can travel long distances graded potentials that are local membrane changes only

EPSP and IPSP

Summation Spatial Summation If several presynaptic end bulbs release their neurotransmitter at about the same time, the combined effect may generate a nerve impulse due to summation Summation may be spatial or temporal. Spatial Summation Summation of effects of neurotransmitters released from several end bulbs onto one neuron Temporal summation: Summation of effect of neurotransmitters released from 2 or more firings of the same end bulb in rapid succession onto a second neuron