抄録
In sympathetic nerve endings, N-, P/Q- and L-type Ca2+ channels are present and contribute to the release of noradrenaline. The N-type channel is composed of several subunits including a pore forming subunit, α1B, and accessory β subunits. To investigate the role of the N-type channel in positive inotropic response of cardiac muscle resulting from stimulation of the sympathetic nerves, we have analyzed β3-null (β3-/-), β3-transgenic (β3-Tg), α1B-null (α1B-/-) and wild-type (WT) mice by measuring isovolumic contraction of left ventricle using a Langendorff apparatus. The positive inotropic effect of field stimulation was significantly reduced in α1B-/- and β3-/- mice, but enhanced in β3-Tg mice, when compared to WT mice. The positive inotropic effect of field stimulation was almost completely abolished by ω-conotoxin GVIA in β3-/- and β3+/+ mice, but was only slightly inhibited in α1B-/- mice. On the other hand, ω-agatoxin IVA had no effect on the positive inotropic effect of field stimulation. Furthermore, voltage-dependent Ca2+ current, recorded in isolated ventricular cells of β3-/-, β3-Tg and WT mice, had essentially similar kinetic properties and response to beta-adrenergic stimulation. These results indicate that the N-type channel plays a major role in Ca2+ entry in sympathetic nerve terminals, and that β3 subunit constitutes N-type channels together with α1B subunit. [Jpn J Physiol 55 Suppl:S96 (2005)]
