Abstract
SummaryFunctional connectivity between brain regions relies on long-range signaling by myelinated axons. This is secured by saltatory action potential propagation that depends fundamentally on sodium channel availability at nodes of Ranvier. Although various potassium channel types have been anatomically localized to myelinated axons in the brain, direct evidence for their functional recruitment in maintaining node excitability is scarce. Cerebellar Purkinje cells provide continuous input to their targets in the cerebellar nuclei, reliably transmitting axonal spikes over a wide range of rates, requiring a constantly available pool of nodal sodium channels. We show that the recruitment of calcium-activated potassium channels (IK, KCa3.1) by local, activity-dependent calcium (Ca2+) influx at nodes of Ranvier via a T-type voltage-gated Ca2+ current provides a powerful mechanism that likely opposes depolarizing block at the nodes and is thus pivotal to securing continuous axonal spike propagation in spontaneously firing Purkinje cells.
Highlights
Understanding information transmission within neuronal circuits, and the factors underlying long-range axonal signaling malfunction, relies on identifying the axonal ion channels that are key regulators of node of Ranvier (NoR) excitability
Various potassium channel types have been anatomically localized to myelinated axons in the brain, direct evidence for their functional recruitment in maintaining node excitability is scarce
We show that the recruitment of calcium-activated potassium channels (IK, KCa3.1) by local, activity-dependent calcium (Ca2+) influx at nodes of Ranvier via a T-type voltage-gated Ca2+ current provides a powerful mechanism that likely opposes depolarizing block at the nodes and is pivotal to securing continuous axonal spike propagation in spontaneously firing Purkinje cells
Summary
Understanding information transmission within neuronal circuits, and the factors underlying long-range axonal signaling malfunction, relies on identifying the axonal ion channels that are key regulators of node of Ranvier (NoR) excitability. The repolarizing currents required to sustain Nav availability at NoRs for reliable AP transmission is less clear cut, in the mammalian brain. Both low- and high-voltage-activated potassium (K+) channel subunits (Kv7 and Kv3.1/3) have been anatomically localized to NoRs (Devaux et al, 2003, 2004; Pan et al, 2006), and their presence can vary between brain regions and axon types (Debanne et al, 2011; Devaux et al, 2003, 2004), recent experiments provide direct evidence that Kv7 channels stabilize NoR membrane potential (Vm) in cortical. Cavs have been proposed to influence NoR formation during development (Alix et al, 2008), their presence at mature NoRs in the brain is not established (Zhang et al, 2006)
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