EFFECTS OF SOME ORGANIC CALCIUM ANTAGONISTS AND OTHER PROCEDURES AFFECTING Ca2+ TRANSLOCATION ON KCl-INDUCED CONTRACTIONS IN THE RAT VAS DEFERENS

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Abstract
1 Both phasic and tonic responses to KCl 160 mm were reduced by Ca2+ deprivation. After 90 min, the phasic response was abolished but 13 ± 1.5% of the tonic response remained. This resistant component was still present if the Ca2+-free solution contained EGTA 0.1 mm. The tonic response was more resistant to deprivation in the prostatic half, while the phasic was more resistant in the epididymal half. KCl-induced contractions were completely restored 5 min after readmission of Ca2+. 2 Both the phasic and the tonic responses were reduced on lowering, and increased on raising [Ca2+]o. In 0.1 mm Ca2+, the phasic response was abolished, but 23 ± 4% of the tonic response remained (mainly attributable to the prostatic half). These resistant contractions indicate that some of the extracellular Ca2+, especially in the prostatic half, is bound with high affinity, probably to the plasma membrane. 3 Incubation with LaCl3 (0.3–10 mm) for 15 min inhibited the phasic response more than the tonic. After incubation for 1 h, 3 mm LaCl3 abolished both phases. It is concluded that La3+ blocks Ca2+ channels most readily when they are opened during the spike. Hydralazine (0.76–5.1 mm) resembled LaCl3 in that it reduced the phasic response with little effect on the tonic. 4 MnCl2 (0.3–10 mm) reduced the phasic but increased the tonic response at all concentrations. The augmenting effect may be due to release of intracellular Ca2+ or to inhibition of Ca2+ efflux. 5 The tonic response was inhibited more than the phasic response by nifedipine (0.002–0.01 μm), methoxyverapamil (0.06–2 μm), verapamil (0.2–1 μm), flunarizine (0.2–100 Iμm)and diazoxide (22–650 μm). With higher concentrations, only flunarizine remained selective for the tonic response. It is concluded that flunarizine blocks Ca2+ channels most readily when opened during sustained spike-free depolarization. 6 Methoxyverapamil 48 μm and verapamil 100 μm virtually abolished both phases of the contraction to KCl 160 mm, but no more than 80% inhibition could be produced with nifedipine. It is concluded that voltage-sensitive Ca2+ channels exist in two sub-types, one of which is blocked by nifedipine, and both are blocked by verapamil, methoxyverapamil and flunarizine. Nitroprusside 17 μm had no effect on the phasic response but inhibited the nifedipine-resistant component of the tonic response. 7 Increasing [Ca2+]o reversed the effects of verapamil, methoxyverapamil, nifedipine and MnCl2, but not the effects of LaCl3. 8 Dantrolene sodium (1.25–25 μm) had no effect on KCl-induced contractions.

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