Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.
Journal of Neuroscience. 2014-03-05; 34(10): 3719-3732
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1. J Neurosci. 2014 Mar 5;34(10):3719-32. doi: 10.1523/JNEUROSCI.4206-13.2014.
Heteromeric Kv7.2/7.3 channels differentially regulate action potential
initiation and conduction in neocortical myelinated axons.
Battefeld A(1), Tran BT, Gavrilis J, Cooper EC, Kole MH.
(1)Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences,
1105 BA, Amsterdam, The Netherlands, Baylor College of Medicine, Baylor Plaza,
Houston, Texas 77030, Eccles Institute for Neuroscience, The Australian National
University, Canberra 0200, Australian Capital Territory, Australia, and
Department of Audiology and Speech Pathology, University of Melbourne, Melbourne,
Victoria 3010, Australia.
Channels (Austin). 2014;8(4):288-9.
Rapid energy-efficient signaling along vertebrate axons is achieved through
intricate subcellular arrangements of voltage-gated ion channels and myelination.
One recently appreciated example is the tight colocalization of K(v)7 potassium
channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment
and nodes of Ranvier. The local biophysical properties of these K(v)7 channels
and the functional impact of colocalization with Na(v) channels remain poorly
understood. Here, we quantitatively examined K(v)7 channels in myelinated axons
of rat neocortical pyramidal neurons using high-resolution confocal imaging and
patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within
the distal two-thirds of the axon initial segment and was mirrored by the
conductance density estimates, which increased from ~12 (proximal) to 150 pS
μm(-2) (distal). The axonal initial segment and nodal M-currents were similar in
voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4%
activated at the resting membrane potential and rapidly activated with
single-exponential time constants (~15 ms at 28 mV). Experiments and
computational modeling showed that while somatodendritic K(v)7 channels are
strongly activated by the backpropagating action potential to attenuate the
afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally
recruited by the forward-propagating action potential. Instead, in nodal domains
K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action
potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7
clustering near axonal Na(v) channels serves specific and context-dependent
roles, both restraining initiation and enhancing conduction of the action
PMID: 24599470 [Indexed for MEDLINE]