T- and L-type calcium channels mediate alpha(1)-adrenoceptor-evoked contraction in the guinea-pig vas deferens.

Aims: The importance of the T- and L-type Ca(2+) channels on the alpha(1)-adrenoceptor-mediated contraction of guinea-pig vas deferens was investigated in relation to the SK and BK channels.

Methods: Isometric contractile response to electrical stimulation (ES) of 50 pulses at 40 Hz was recorded. ES responses were modulated via calcium and potassium channels in the presence of purinergic inhibitors.

Results: The alpha(1)-adrenoceptor-mediated contraction of guinea-pig vas deferens consisted of early and late alpha(1)-components. The early alpha(1)-component was insensitive to nifedipine (10 microM) but was suppressed by T-type Ca(2+) channel antagonists mibefradil and amiloride with IC50 values (microM) of 7.2 +/- 1.8 (n = 5) and 27.2 +/- 10.4 (n = 6), respectively. The late alpha(1)-component was inhibited by nifedipine, nimodipine and nicardipine with IC50 values (microM) of 0.19 +/- 0.04 (n = 5), 1.9 +/- 0.8 (n = 5), and 4.2 +/- 2.5 (n = 5), respectively. Nicardipine also inhibited the early alpha(1)-component with an IC50 value of 20.3 +/- 2.5 microM (n = 5). An SK channel antagonist apamin (1-100 nM) increased both early and late alpha(1)-components. A BK channel antagonist iberiotoxin (100 nM) increased the late alpha(1)-component without affecting the early one.

Conclusions: The results may indicate that the alpha(1)-adrenoceptor-induced contraction was mediated by Ca(2+) influx through T- and L-type Ca(2+) channels for the early and late alpha(1)-components, respectively and that SK and BK channels contributed to protect the musculature of the guinea-pig vas deferens from excess tension development induced by sympathetic volley. Neurourol. Urodynam. 28:447-454, 2009. (c) 2009 Wiley-Liss, Inc.