• Voltage Dependent Channels open with change of Em (depolarization)
• Small flux across membrane causes depolarization; concentration remains unaffected
• Channels are time dependent because depolarization => change in the rate constant for open/closed conformational equil
• Since rate is a function of time we say that these channels are then time dependent because time is required to reach equilibrium
• Single channel still behaves randomly; however, probability of being open shifts from likely closed to likely open
• Reversal potential is E_k+ -concentration gradient
• Current is out (up by convention)

• Reversal Potential = E_Na+ -concentration and electrical potential
• Na⁺ has Greater driving force
• gates open faster (sooner) than K⁺ (i.e., first)
• Gate closes quickly due to Inactivation (conceptually incompatible with open/closed model)

K⁺ vs Na⁺ Channels – closed-open-inactivated (C-O-I) model

Hodgkin Huxley Model – Voltage Clamp Experiments

• Key ideas:
• (1) Separate Na⁺/K⁺ permiabilities
• (2) Voltage controls transitions between closed, open and inactivated
• Determined the time course of Na⁺/K⁺ conductance at different voltages
• increased voltage:
• (1) increased # of channels that open
• (2) decreased time for channels to open
• (3) decreased time for Na⁺ channel to inactivate
• Na⁺ channels dominate 0-1ms; K⁺ channels dominate 1+ ms
• K⁺ Channel Model:
• Opens with sigmoid time course – delayed rectifier
• 4 identical, independent gates
• all must be open to open channel
• n = probability that any gate is open
• n⁴ = probability that all 4 are open (channel open)
• Na⁺ Channel Model
• Open with sigmoid time course, but 10X faster than K+
• 4 independent gates
• 3 identical gates that open with depolarization / probability of being open = m
• 1 independent inactivation gate closed with depolarization / probability of being open = h
• closes slower than m’s open î inactivation independent ( unlike C-O-I model)
• probability that the channel is open = m³h
• at resting potential h=open m= closed / depolarization = m’s open fast and h closes slowly
• Action Potential
• Eo to threshold produces action potential (regenerative response); cell then becomes hyperpolarized since K⁺ channels still open (afterhyperpolarization), then back to Eo
• Positive Feedback (up stroke) : Depolarization Þ Na⁺ influx Þ depolarization Þ channels open Þ depolarization
• Negative Feedback (down stroke): Depolarization Þ open K⁺ channels Þ polarization Þ Na⁺ channel opening Þ hyperpolarization
• K⁺ Channels are diverse. Regulate: Eo, repolarization, E_Th, , Adaptation ( = ¯ ¦ AP during a maintained stimulus)

Voltage Dependent Ca⁺⁺ Channels – cause increased [Ca⁺⁺] in cell