An Eye On Ion Channels

Milton puts an eye on

I o n C h a n n e l s

General Ion Channels

Voltage-Gated Na⁺ Channel

· Three possible states: Resting, Active & Inactive

· Activates quickly / Inactivates slowly (Activation occurs first even though it is at a higher potential than Inactivation because it is faster)

· Returns to Resting only when re-polarized

· Tetrodotoxin sensitive

Voltage-Gated Ca⁺⁺ Channel

· Similar to Voltage-Gated Na⁺ Channel

Delayed Rectifier1 K⁺ Channel

· Voltage-Gated (Activated at threshold, but since it’s slow, doesn’t open until a little later, causing repolarization)

· Two states: Resting & Active (Note: Other K+ Channels can be Inactivated)

SA Node Ion Channels

H Channel (I_h)

· Creates Pacemaker Potential (AKA - Phase 4 Depolarization)

· Voltage-Gated: Activated by Hyperpolarization (below -32mV)

· “Cation Current” (Dr. Tarr didn’t specify which cation, but Guyton says Na⁺)

· (+) by NE (Depolarizing Shift allows H Channels to start opening at higher potentials, thus allowing them to activate sooner and bring about the next Action Potential sooner)

· (-) by ACh (Hyperpolarizing Shift delays onset, thus slowing pacemaker)

Delayed Rectifier K⁺ Channel (I_K)

· Delayed opening from Threshold

· Repolarizes cell

· (+) by NE (Returns cell to polarized state faster, thus shortening duration of the AP and bringing about the next AP sooner)

T-Type Ca⁺⁺ Channel (I_Ca,T)

· Most are activated during the latter part of Pacemaker Potential (ie - before threshold)

· The rest are activated at Threshold (with the L-Type)

L-Type Ca⁺⁺ Channel (I_Ca,L)

· Opens at Threshold; responsible for the full AP

· (+) by NE (Depolarizing Shift allows L-Type Ca⁺⁺Channels to open sooner with a lower threshold)

Muscarinic K⁺ Channel (I_K(ACh))

· Activated only by high levels of ACh

· Causes a Hyperpolarizing Shift of SA Node by K⁺ efflux, thus slowing (or even stopping) the heart

Ventricular Muscle Ion Channels

Note: Dr. Tarr didn’t specify what channel is responsible for the Action Potential depolarization of ventricular muscle (ie - Na⁺, Ca⁺⁺, both?). The following three channels, however are responsible for the long-duration repolarization.

Slow Inactivating Ca⁺⁺ Channel

· Slow to inactivate, therefore Ca⁺⁺ influx continues to help sustain the plateau

Inward Rectifier K⁺ Channel

· Closes when potential rises 20-30 mV above threshold (Note: This is opposite of the Delayed Rectifier K⁺ Channels which open with depolarization.)

· This closure allows the Ca⁺⁺ influx to predominate & sustain the plateau

Delayed Rectifier K⁺ Channel

· Just like before except these are even more delayed (100-300 msec)

Neuron Soma Ion Channels

A-Type K⁺ Channel (I_A)

· Activation will delay the Interspike Interval thus slowing each AP and decreasing the firing rate

· Half-Inactivation -75mV / Half-Activation -40mV (I’m not sure how these help us.)

· Time Component & Stimulus Size: Let’s assume that any stimulus that is large enough to reach the Na⁺ Channel threshold will also activate this A-Type K⁺ Channel. With small stimuli, the A-Type Channels will activate and are slow to inactivate. Thus they are allowed to slow the depolarization (ie- longer Interpulse Interval). Large stimuli also activate the A-Type Channels, but they are able to quickly inactivate them as well. This prevents them from slowing the depolarization. Therefore, shorter Interpulse Interval. And Viola! Faster overall firing rate!

· (-) by 4-Aminopyridine

Ca⁺⁺-Gated K⁺ Channels

· Spike Frequency Adaptation: Ca⁺⁺ influx during AP’s allows K⁺ efflux which gives an “afterhyperpolarization” that causes the neuron to quit responding to a prolonged stimulus (eg- ignore your watchband)

· Two Types:

1. BK (I_C): Big conductance; responsible for early part of afterhyperpolarization

2. SK (I_AHP): Small conductance; responsible for late part of afterhyperpolarization

Note: All three of these channels modulate neuronal response to a constant stimulus. Only the Ca⁺⁺-Gated K⁺ Channels (BK & SK) give Spike Frequency Adaptation.

And to confuse things even more…

Neuro Ion Channels in the Axon Hillock (Levine’s Handout, pg 47)

Slow Voltage-Gated K⁺ Channel

· Same as Physiology’s “Delayed Rectifier”

Early Voltage-Gated K+ Channel

· Allows rapid firing rate for large stimuli (Stays open with small stimuli that just barely reach threshold thus reducing rate of depolarization and slowing total time for Action Potentials. With large stimuli, it closes thus making for a fast AP that can be quickly repeated)

· Sounds the same as Physiology’s A-Type K⁺ Channel

Ca⁺⁺-Gated K⁺ Channel

· Adaptation to repeated stimuli (When Ca⁺⁺ builds up from its channel, it allows K⁺ efflux which hyperpolarizes the cell to adapt to repeated stimuli)

Voltage-Gated Ca⁺⁺ Channel

· Plays role in adaptation (and I assume depolarization)

Voltage-Gated Na⁺ Channel

· Our friend, Mr. Action Potential Generator, himself (Just don’t confuse him for the Ligand -Gated Na⁺ Channels at the Dendrites and Soma)