Effect of adrenergic agonists on Ca2+-channel currents in single vascular smooth muscle cells

Ca2+-channel currents have been measured in enzymatically dispersed single smooth muscle cells of the rabbit ear artery using the whole-cell patch clamp technique. Inward currents were elicited by depolarizing test pulses from a holding potential of -50 mV. These currents were activated from -30 mV onward and reached full activation around 0 mV. alpha-Adrenergic agonists did not affect the background current measured at the holding potential, but markedly reduced the peak amplitude of the voltage-activated Ca2+-channel currents. This alpha-adrenergic inhibition also occurred in cells which were internally perfused with solutions containing either 10 microM cAMP, 10 microM cGMP or 0.1 mM GTP, but became irreversible when the pipette solution contained a non-hydrolyzable GTP-analog. The action of beta-agonists on the voltage-activated Ca2+-channel currents was variable, and ranged from no effect at all to a 50% reduction of the current. It is concluded that alpha-agonists do not open receptor-operated Ca2+-channels in these smooth muscle cells. The inhibition of the voltage-activated Ca2+-currents does not seem to be mediated through changes in cyclic nucleotide levels, but might be mediated through G-proteins. Its physiological relevance remains however unclear. The action of beta-agonists is consistent with their relaxing effect, but the reason for the non-uniform response has not been elucidated.