Nerve Excitation Topic II2 Biophysics Neurons Motor neuron

Nerve Excitation Topic II-2 Biophysics

Neurons Motor neuron Sensory neuron • Nerve signals due to modulations of membrane potential • Motor Neurons have dendrites

History § Action potential is electrical pulse that travels much slower than electrical current §K+ and especially Na+ play big role Calamari Andrew Fielding Huxley Alan Lloyd Hodgkin §Hodgkin and Katz: as [Na+] decreases velocity of action potential decreases • Hodgkin and Huxley observe membrane potential reverses during pulse and goes to +100 m. V • They also see that conductance of membrane increases 40 X and propose have transient changes in Na and K conductance → Nobel Prize

Voltage Clamp Positive current: + ions out of axon VK = -72 m. V, VNa = + 55 m. V DV = Vin - Vout • • • Measure current to keep voltage constant INa = g. Na(Vm – VNa), IK = g. K(Vm -VK), IL = g. L(Vm – Vk) Voltage Clamp makes IC = Cm d. V/dt = 0 Itot = INa + IK + IL (with clamp) Vm = Vh = 1/gtot (g. KVK + g. Na. VNa + g. LVL + I), clamp and look at I

Voltage Clamp experiments • Set concentrations of ions so can get Nernst potentials equal membrane potential and reduce variables • g. Na, g. K ~ 0 at resting potential and they are only activated when the axon is depolarized (becomes less negative). H&H get g. L when hyperpolarize • I = IL = g. L (Vm – VL), VL < Vresting (-60 m. V)

Action Potential 1. Resting Na m gate closed h gate open; n-gate closed 2. Sufficient initial depolarization → open m-gate, Vm → VNa; h 3. h gate closes (inactivation) and K n -gate opens, Vm → Vk 4. n-gate closes and h-gate opens (de -inactivation), Vm → Vrest Do Axon 1 Dynamics

H&H Voltage Clamp experiments • When depolarize, get early negative current and later positive current • As DV increases • Amplitude of Ineg decreases; DV = 117 have Ineg = 0; DV > 117 have early positive current • Rate of current development increases (both + and -) • Switch from negative current to positive gets earlier • Note: VK = -72 m. V, VNa = +55 m. V, Vresting = -60 m. V; INa = g. Na(Vm – VNa), IK = g. K(Vm – VK) • So IK always positive; INa negative for small DV but becomes positive for DV>115 m. V • I reversal could be due to cessation of early I- or stronger/earlier I+ • H&H isolate currents by setting Vm = VNa so get voltage dependence of IK • Deduce voltage dependence of INa since Itot = INa + IK Do Axon 2&3 Voltage Clamp Currents

Na activation and inactivation and deinactivation §DV activation , time inactivation deinactivation is also voltage dependent §H&H use conditioning steps: §Brief conditioning depolarization reduced INa during 2 nd step §As Dt for conditioning step increases INa 2 nd step decreases (more sodium channels inactivated during conditioning step) H&H find time and voltage dependence of inactivation ex – conditioning step + 29 m. V tinactivation = 2 ms (nearly complete) step + 8 m. V tinactivation > 8 ms (less inactivation) They found that even at resting potential, many sodium channel are inactive. § H&H used long conditioning steps to study de-inactivation This turned off (closed) Na channels then set 2 nd voltage to recovery voltage – vary time to 3 rd voltage to look at current. Do Axon 4 Voltage Clamp Na Inact

Empirical Equations §Generally dg/dt = a(1 -g) – bg; a = opening (fwd rate), b = closing §Potassium, have gk = gkmaxn 4; gkmax = max conductance (all open) Do Axon 5 §Sodium, have g. Na = g. Namaxm 3 h, m is like n for K, h describes inactivation Voltage Clamp Na K §Each has time dependence like n conductance §m 3 = fraction activated, h is fraction de-inactivated If know parameters (max g, taus, nernst potentials etc) can get action potential and explain all observed phenomenon.

Action Potential Do Axon 6 Impulse conductance

Threshold and Refractory Period http: //www. biocrawler. com/encyclopedia/Action_potential http: //cwx. prenhall. com/bookbind/pubbooks/morris 5/medialib/images/F 02_03. gif §There is a minimum initial depolarization you need to get action potential – this is the threshold. “All or none” aspect of action potential §After action potential, threshold is infinity (Na h gates closed), this leads to a refractory period. Do Axon 7&8 Impulse Threshold and Refractory

Spread of Action Potential http: //www. arts. uwaterloo. ca/~bfleming/psych 261/image 25. gif §Na comes in and causes depolarization at neighboring sites. Refractory period insures unidirectional event. §Want current to go along axon, not out of axon §Invertebrates: large radius → small R §Vertebrates: large R along axon (myelin sheath and nodes of Ranier)

• Have ligand gated channel (eg Ach receptor that needs two Ach to open). • When open both Na and K can get through → get depolzarization