CALCIUM DEPENDENCE OF CONTRACTILE ACTIVATION OF ISOLATED SHEEP URETHRA .1. RESPONSES TO ELECTRICAL-STIMULATION

In isolated sheep urethral smooth muscle at resting tension, responses elicited by electrical stimulation of nerves were either contraction (40%), or contraction preceded by relaxation (60%). All responses were suppressed by tetrodotoxin (TTX), but at stimulation frequencies exceeding 16 Hz, there was a small TTX resistant contraction, which at the highest frequency used (50 Hz) amounted to about 15% of the total response. alpha-Adrenoceptor blockade suppressed the contractions, as did chemical sympathectomy with 6-hydroxydopamine. In calcium-free medium all electrically induced contractions were abolished. Nifedipine, verapamil, and lanthanum had concentration-dependent depressant actions, whereas Bay K 8644 (10(-6) M) significantly increased the responses. In preparations prelabelled with H-3-noradrenaline, electrical stimulation caused a release of H-3 that could be blocked by TTX, and effectively reduced by calcium-free medium and lanthanum. However, the release was unaffected by nifedipine, and moderately reduced by high concentrations of verapamil (10(-5) M). It is suggested that contractile responses to electrical stimulation in isolated sheep urethral smooth muscle are mediated by the sympathetic nervous system, mainly through release of noradrenaline stimulating postjunctional alpha-1-adrenoceptors. The release of noradrenaline, as well as the action of released noradrenaline on postjunctional membranes are calcium-dependent. However, the calcium entry pathways used are partly different from those inhibited by organic calcium antagonists.