ROLE OF N-TYPE, P-TYPE AND Q-TYPE VOLTAGE-GATED CALCIUM CHANNELS IN TRANSMITTER RELEASE FROM SYMPATHETIC NEURONS IN THE MOUSE ISOLATED VAS-DEFERENS

1 N-type voltage-gated calcium channels are known to play an important role in transmitter release from autonomic neurones, and recent studi es have demonstrated that non-N-type calcium channels are also involve d. The calcium channels coupled to transmitter release from sympatheti c neurones in the mouse isolated vas deferens were investigated in the present study. 2 Contractions of the mouse vas deferens were evoked b y electrical stimulation at 1-50 Hz. The contractions were entirely ne rve-mediated, since they were abolished by tetrodotoxin, and were used as an indirect measure of transmitter release. 3 The N-type calcium c hannel blocker, omega-conotoxin GVIA, inhibited contractions in a conc entration-dependent manner, with a maximal effect at 30 nM. Contractio ns evoked by stimulation frequencies less than 10 Hz were abolished, a nd those evoked by 20 and by 50 Hz stimulation were decreased in ampli tude by 51.3+/-13.9% and 9.3+/-2.6%, respectively. 4 The N-, P- and Q- type channel blocker, omega-conotoxin MVIIC, inhibited contractions in a concentration-dependent manner and caused greater maximum inhibitio n than omega-conotoxin GVIA, suggesting an action on P- and/or Q-type channels, in addition to N-type. 5 The P-type channel blocker, omega-a gatoxin IVA, alone did not have a significant effect at concentrations up to 300 nM, but inhibited contractions in the presence of omega-con otoxin GVIA. Subsequent addition of omega-conotoxin MVIIC abolished th e remaining contractions. Identical results were obtained when the thr ee toxins were tested cumulatively on the purinergic and noradrenergic components of the contraction in the presence of 0.3 mu M prazosin an d following desensitization to 10 mu M alpha,beta-methylene adenosine 5'-triphosphate (alpha,beta-MeATP), respectively. 6 The results sugges t that N-, P- and Q-type channels are involved in the release of norad renaline and ATP from sympathetic neurones in the mouse vas deferens.