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

Abstract

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 ®eld stimulation (trains of ®ve stimuli at 0.9 Hz) in small mesenteric arteries. The average resting membrane potential was 759.8+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 mM) or by o-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 mM, a concentration su cient to abolish the contraction to potassium depolarization. However, mibefradil (3 mM), 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 ®nding that Ni 2+ (300 mM), 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.

N-type and P/Q-type calcium channels regulate differentially the release of noradrenaline, ATP and β-NAD in blood vessels

“…On the other hand, the present results are in contrast to studies reporting that the release of ATP in rat tail artery (Brock and Cunnane, 1999), rat mesenteric artery (Xi et al, 2002), determined by changes in the EFS-elicited excitatory junction potentials, or cultured sympathetic neurons (von Kugelgen et al, 1994) is significantly reduced by ω-CTX GVIA. One might argue that sources other than sympathetic nerves may be involved in the release of ATP in the overflow experiments.…”

Involvement of Different Calcium Channels in the Depolarization‐Evoked Release of Noradrenaline from Sympathetic Neurones in Rabbit Carotid Artery*

“…Our findings ( fig. 6 and 7) are in line with the conclusion that mibefradil is not a blocking agent of N-type Ca 2π channels (Xi & Angus 2001;Xi et al 2002).…”

T-type Ca2+ channels in non-vascular smooth muscles

“…A role for transmembrane Ca 2+ influx has been implicated in this overall scheme, but the route is not known. Both Ni 2+ (50 µM) and mibefradil were ineffective in attenuating EJPs or intracellular Ca 2+ transients, suggesting that the T-type channel is not involved [67,68]. This contrasts to a study with mesenteric blood vessels, which showed the Ni 2+ did attenuate EJPs [68] and shows that similar phenomena are regulated by alternative processes in different cells.…”