Excitatory and inhibitory actions of norepinephrine on the Ba2+ current through L-type Ca2+ channels of smooth muscle cells of guinea-pig vas deferens.

Abstract

The effect of norepinephrine (NE) was examined on the whole-cell Ba2+ current through L-type Ca2+ channels of freshly isolated smooth muscle cells of guinea-pig vas deferens. The magnitude of maximum Ba2+ current [1Ba(max)] varied in different cells, although the capacitance of the cell membrane was similar (approximately 50 pF). Application of dbcAMP augmented 1Ba(max) by 37%, which was canceled by Rp-cAMPs, while PMA decreased the current by 32%, which was canceled by staurosporine. NE increased 1Ba(max) of the cells which originally showed relatively small 1Ba(max), and decreased the current of the cells which showed larger 1Ba(max). In the presence of phentolamine, NE increased 1Ba(max), and this effect was remarkable in cells showed smaller 1Ba(max). In the presence of propranolol, NE decreased 1Ba(max). The excitatory beta-adrenoceptor activation was canceled by Rp-cAMPs, and the inhibitory alpha-adrenoceptor effect was canceled by staurosporine. It is suggested that NE shows dual (excitatory and inhibitory) actions on the L-type Ca2+ channels of smooth muscle of guinea-pig vas deferens. The excitatory beta-adrenoceptor action mediated through cAMP/PKA is predominant in cells with lower density of the Ca2+ channels, while inhibitory alpha-adrenoceptor action mediated through PKC is predominant in cells with higher channel density.