Involvement of T-type calcium channels in excitatory junction potentials in rat resistance mesenteric arteries.

1. We investigated the role of voltage-operated calcium channels in sympathetic transmission and depolarization-induced contractions in the rat mesenteric artery. In particular, we investigated the role of the T-type voltage-operated calcium channels (T-channels) in mediating excitatory junction potentials (EJPs). 2. EJPs were evoked by electrical field stimulation (trains of five stimuli at 0.9 Hz) in small mesenteric arteries. The average resting membrane potential was -59.8+/-0.5 mV (n=65). Trains of stimuli evoked individual EJPs with the peak EJP of 6+/-0.2 mV (n=34) occurring with the second stimulus. Trains of EJPs were inhibited 90% by tetrodotoxin (0.1 micro M) or by omega-conotoxin GVIA (GVIA, 10 nM) indicating their neural origin. 3. The EJPs were not inhibited by the L-type calcium channel blocker nicardipine at 0.1 micro M, a concentration sufficient to abolish the contraction to potassium depolarization. However, mibefradil (3 micro M), considered a relatively selective T-channel antagonist, inhibited the EJPs by about 50%. This concentration of mibefradil did not inhibit GVIA-sensitive electrically-evoked twitches of the rat vas deferens. Thus the action of mibefradil in reducing EJPs is unlikely to be due to either inhibition of L- or N-type channels but is probably due to inhibition of T-channels. 4. The finding that Ni(2+) (300 micro M), an inhibitor of T-type calcium channels, also reduced EJP amplitude by about 80% but did not block electrically-evoked twitches in the rat vas deferens, further supports an important role of T-channels in mediating small depolarizations associated with the EJPs evoked by sympathetic nerve stimulation.