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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
- 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
- Namkung, Y; Smith, SM; Lee, SB; Skrypnyk, NV; Kim, HL; Chin, H; Scheller, RH; Tsien, RW; Shin, HS
- Ewha Authors
- SCOPUS Author ID
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- Journal Title
- PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
- vol. 95, no. 20, pp. 12010 - 12015
- NATL ACAD SCIENCES
- SCI; SCIE; SCOPUS
- 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.
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