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Targeted disruption of the Ca2+ channel beta(3) subunit reduces N- and L-type Ca2+ channel activity and alters the voltage-dependent activation of P/Q-type Ca2+ channels in neurons

Title
Targeted disruption of the Ca2+ channel beta(3) subunit reduces N- and L-type Ca2+ channel activity and alters the voltage-dependent activation of P/Q-type Ca2+ channels in neurons
Authors
Namkung, YSmith, SMLee, SBSkrypnyk, NVKim, HLChin, HScheller, RHTsien, RWShin, HS
Ewha Authors
김형래
SCOPUS Author ID
김형래scopus
Issue Date
1998
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
ISSN
0027-8424JCR Link
Citation
vol. 95, no. 20, pp. 12010 - 12015
Publisher
NATL ACAD SCIENCES
Indexed
SCI; SCIE; SCOPUS WOS
Abstract
In comparison to the well characterized role of the principal subunit of voltage-gated Ca2+ channels, the pore-forming, antagonist-binding alpha(1) subunit, considerably less is understood about how beta subunits contribute to neuronal Ca2+ channel function. We studied the role of the Ca2+ channel beta(3) subunit, the major Ca2+ channel beta subunit in neurons, by using a gene-targeting strategy. The beta(3) deficient (beta(3)-/-) animals were indistinguishable from the wild type (wt) with no gross morphological or histological differences. However, in sympathetic beta 3-/- neurons, the L- and N-type current was significantly reduced relative to wt. Voltage-dependent activation of P/Q-type Ca2+ channels was described by two Boltzmann components with different voltage dependence, analogous to the "reluctant" and "willing" states reported for N-type channels. The absence of the beta(3) subunit was associated with a hyperpolarizing shift of the "reluctant" component of activation. Norepinephrine inhibited wt and beta(3)-/- neurons similarly but the voltage sensitive component was greater for N-type than P/Q-type Ca2+ channels, The reduction in the expression of N-type Ca2+ channels in the beta(3)-/- mice may be expected to impair Ca2+ entry and therefore synaptic transmission in these animals. This effect may be reversed, at least in part, by the increase in the proportion of P/Q channels activated at less depolarized voltage levels.
DOI
10.1073/pnas.95.20.12010
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의학전문대학원 > 의학과 > Journal papers
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