T‐ and L‐type calcium channels mediate α 1 ‐adrenoceptor‐evoked contraction in the guinea‐pig vas deferens

Aims The importance of the T‐ and L‐type Ca 2+ channels on the α 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 α 1 ‐adrenoceptor‐mediated contraction of guinea‐pig vas deferens consisted of early and late α 1 ‐components. The early α 1 ‐component was insensitive to nifedipine (10 µM) but was suppressed by T‐type Ca 2+ channel antagonists mibefradil and amiloride with IC50 values (µM) of 7.2 ± 1.8 (n = 5) and 27.2 ± 10.4 (n = 6), respectively. The late α 1 ‐component was inhibited by nifedipine, nimodipine and nicardipine with IC50 values (µM) 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 α 1 ‐component with an IC50 value of 20.3 ± 2.5 µM (n = 5). An SK channel antagonist apamin (1–100 nM) increased both early and late α 1 ‐components. A BK channel antagonist iberiotoxin (100 nM) increased the late α 1 ‐component without affecting the early one. Conclusions The results may indicate that the α 1 ‐adrenoceptor‐induced contraction was mediated by Ca 2+ influx through T‐ and L‐type Ca 2+ channels for the early and late α 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. © 2009 Wiley‐Liss, Inc.