T-type CaV3.3 calcium channels produce spontaneous low-threshold action potentials and intracellular calcium oscillations.
European Journal of Neuroscience. 2006-05-01; 23(9): 2321-2329
DOI: 10.1111/j.1460-9568.2006.04761.x
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1. Eur J Neurosci. 2006 May;23(9):2321-9.
T-type CaV3.3 calcium channels produce spontaneous low-threshold action
potentials and intracellular calcium oscillations.
Chevalier M(1), Lory P, Mironneau C, Macrez N, Quignard JF.
Author information:
(1)Laboratoire de Signalization et Interactions cellulaires, CNRS UMR 5017,
Université Bordeaux II, UFR Sciences Pharmaceutiques, 146 rue Léo Saignat, 33076
Bordeaux cedex, France.
The precise contribution of T-type Ca2+ channels in generating action potentials
(APs), burst firing and intracellular Ca2+ signals needs further elucidation.
Here, we show that CaV3.3 channels can trigger repetitive APs, generating
spontaneous membrane potential oscillations (MPOs), and a concomitant increase in
the intracellular Ca2+ concentration ([Ca2+]i) when overexpressed in NG108-15
cells. MPOs were dependent on CaV3.3 channel activity given that they were
recorded from a potential range of -55 to -70 mV, blocked by nickel and
mibefradil, as well as by low external Ca2+ concentration. APs of distinct
duration were recorded: short APs (sAP) or prolonged APs (pAP) with a plateau
potential near -40 mV. The voltage-dependent properties of the CaV3.3 channels
constrained the AP duration and the plateau potential was supported by sustained
calcium current through CaV3.3 channels. The sustained current amplitude
decreased when the resting holding potential was depolarized, thereby inducing a
switch of AP shape from pAP to sAP. Duration of the [Ca2+]i oscillations was also
closely related to the shape of APs. The CaV3.3 window current was the
oscillation trigger as shown by shifting the CaV3.3 window current potential
range as a result of increasing the external Ca2+ concentration, which resulted
in a corresponding shift of the AP threshold. Overall, the data demonstrate that
the CaV3.3 window current is critical in triggering intrinsic electrical and
[Ca2+]i oscillations. The functional expression of CaV3.3 channels can generate
spontaneous low-threshold calcium APs through its window current, indicating that
CaV3.3 channels can play a primary role in pacemaker activity.
DOI: 10.1111/j.1460-9568.2006.04761.x
PMID: 16706840 [Indexed for MEDLINE]