BK channel activation by L-type Ca2+ channels Ca(V)1.2 and Ca(V)1.3 during the subthreshold phase of an action potential

Plante Amber E.; Whitt Joshua P.; Meredith Andrea L.

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BK channel activation by L-type Ca2+ channels Ca(V)1.2 and Ca(V)1.3 during the subthreshold phase of an action potential

机译：BK channel activation by L-type Ca2+ channels Ca(V)1.2 and Ca(V)1.3 during the subthreshold phase of an action potential

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摘要

Mammalian circadian (24 h) rhythms are timed by the pattern of spontaneous action potential firing in the suprachiasmatic nucleus (SCN). This oscillation in firing is produced through circadian regulation of several membrane currents, including largeconductance Ca2+ - and voltage-activated K+ (BK) and L-type Ca2+ channel (LTCC) currents. During the day steady-state BK currents depend mostly on LTCCs for activation, whereas at night they depend predominantly on ryanodine receptors (RyRs). However, the contribution of these Ca2+ channels to BK channel activation during action potential firing has not been thoroughly investigated. In this study, we used a pharmacological approach to determine that both LTCCs and RyRs contribute to the baseline membrane potential of SCN action potential waveforms, as well as action potential-evoked BK current, during the day and night, respectively. Since the baseline membrane potential is a major determinant of circadian firing rate, we focused on the LTCCs contributing to low voltage activation of BK channels during the subthreshold phase. For these experiments, two LTCC subtypes found in SCN (Ca(V)1.2 and Ca(V)1.3) were coexpressed with BK channels in heterologous cells, where their differential contributions could be separately measured. Ca(V)1.3 channels produced currents that were shifted to more hyperpolarized potentials compared with Ca(V)1.2, resulting in increased subthreshold Ca2+ and BK currents during an action potential command. These results show that although multiple Ca2+ sources in SCN can contribute to the activation of BK current during an action potential, specific BK-Ca(V)1.3 partnerships may optimize the subthreshold BK current activation that is critical for firing rate regulation.

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来源
《Journal of Neurophysiology》 |2021年第2期|427-439|共13页
作者
Plante Amber E.; Whitt Joshua P.; Meredith Andrea L.;
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作者单位

Univ Maryland, Sch Med, Dept Physiol, Baltimore, MD 21201 USA;

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原文格式 PDF
正文语种英语
中图分类人体生理学;
关键词
action potential; BK channel; KCNMA1; L-type calcium channel; suprachiasmatic nucleus;

BK channel activation by L-type Ca2+ channels Ca(V)1.2 and Ca(V)1.3 during the subthreshold phase of an action potential

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