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.
Xi
Qi
Q
Department of Pharmacology, The University of Melbourne, Victoria 3010, Australia.
Ziogas
James
J
Roberts
Jonathan A
JA
Evans
Richard J
RJ
Angus
James A
JA
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D020748:Mibefradil / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology*; D009529:Nicardipine / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects / Q000502:physiology; D014655:Vascular Resistance; D014661:Vasoconstriction / Q000187:drug effects; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D020748:Mibefradil; D013779:Tetrodotoxin; D009532:Nickel; D000255:Adenosine Triphosphate; D020866:omega-Conotoxin GVIA; D009529:Nicardipine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate