Solution (source code)

= Solution

<Voltage> gating and <ion> selectivity are different structural functions. A typical <voltage-gated potassium channel> has four pore-forming subunits; their <Voltage-sensing domain>[voltage-sensing] regions move charged residues in the membrane electric field and couple that motion to a pore gate. Carbonyl coordination in the <selectivity filter> compensates <potassium> dehydration in an ion-specific geometry. The smaller <sodium> <ion> is not automatically passed more readily: its hydration and coordination energetics differ. Structural work on a mammalian Kv channel resolves the sensor/pore architecture and an open activation gate.<Crystal structure of a mammalian voltage-dependent Shaker family K+ channel by Stephen B. Long and others>[Kv1.2 structural study, abstract and open-pore/voltage-sensor architecture]{ref}

A <Voltage-gated sodium channel>[sodium-channel] alpha subunit contains four <Biological homology>[homologous] domains assembled into one pore, with separate <Voltage-sensing domain>[voltage sensors]. Rapid activation and fast <Ion-channel inactivation>[inactivation] are distinguishable conformational transitions; an intracellular <Ion-channel inactivation>[inactivation] apparatus stabilizes nonconducting states after activation. Repolarization favours recovery of availability. A channel can therefore be closed but activatable, or inactivated and temporarily unavailable, despite zero current in both cases.

Several types of evidence test these ideas. Ionic <Reversal potential>[reversal potentials] shift when ionic gradients are changed, establishing selectivity and driving <force>. Single-channel recordings show discrete conducting levels and stochastic dwell times; whole-cell current changes often reflect changed <Two-state ion-channel gating>[open probability] rather than a continuously varying single-channel current. Small <Ion-channel gating current>[gating-charge] transients can remain when ionic permeation is blocked, demonstrating sensor movement rather than <ion> flux. Conditioning and paired-pulse records separate activation, <Ion-channel inactivation>[inactivation] and recovery. Structural perturbations of <Voltage-sensing domain>[voltage sensors] and of <Ion-channel inactivation>[inactivation] machinery alter different kinetic properties, supporting their functional distinction.

These observations constrain models but do not make an individual macroscopic trace a unique structural reconstruction. Different distributions of closed and inactivated states can produce similar averages. In particular, the sustained <potassium> trace supports little <Ion-channel inactivation>[inactivation] on the displayed interval; it does not justify assigning every <Voltage-gated potassium channel>[potassium channel] a universal absence of an <Ion-channel inactivation>[inactivation] mechanism.