标题：Targeted disruption of the Ca2+ channel β3 subunit reduces N- and L-type Ca2+ channel activity and alters the voltagedependent activation of P/Q-type Ca2+ channels in neurons
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：1998
卷号：95
期号：20
页码：12010-12015
DOI：10.1073/pnas.95.20.12010
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In comparison to the well characterized role of the principal subunit of voltage-gated Ca2+ channels, the pore-forming, antagonist-binding 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.
