The relative importance of extracellular and intracellular calcium in the responses of the human vas deferens to noradrenaline and potassium: a study using Ca(2+)-deprivation and Ca(2+)-antagonists.
1. Mechanical responses of the human vas deferens, activated by noradrenaline (50-100 microM) or high potassium (130 mM), showed either biphasic shortening or lengthening or a combination of initial shortening and lengthening. These are interpreted as representing the contractions of longitudinal and circular muscle respectively. 2. Caffeine (10-20 mM) induced only shortening responses which were 86% (SE 34, n = 7) of that caused by noradrenaline (100 microM). 3. The calcium channel antagonists, nifedipine, verapamil and diltiazem (0.01-10 microM), inhibited responses to high potassium, and the initial phase of shortening and lengthening responses to noradrenaline. However, the secondary phase of the shortening response to noradrenaline (100 microM) was relatively insensitive to these antagonists. 4. In calcium-free (1 mM EGTA) media, noradrenaline (100 microM) could repeatedly induce both shortening and lengthening tonic responses which were 39 +/- 13% (n = 4) and 40 +/- 16% (n = 5) of their values in Krebs media. Except for a small shortening, responses to high potassium were abolished. Calcium-free media also blocked phasic bursts of mechanical activity. 5. Calcium removal during a prolonged exposure to noradrenaline (50 microM) caused a fall of tension of the lengthening but not the shortening response. Depletion of intracellular stores caused an inhibition of the responses to noradrenaline. Recovery of responses following restoration of calcium was blocked by nifedipine for the shortening response but not for lengthening. 6. We conclude that longitudinal and circular muscle rely to different degrees on activation by extracellular calcium and intracellular mechanisms. The longitudinal, but not circular, muscle appears mainly to use an intracellular calcium pool which is replenished via nifedipine-sensitive calcium channels and has a caffeine sensitive store. Evidence suggesting differences in the role of calcium and processes controlling its entry during activation of both muscle types is presented and discussed.
Amobi
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Biomedical Sciences Division, King's College London, UK.
Smith
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D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000172:deficiency*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D014649:Vas Deferens / Q000187:drug effects* / Q000502:physiology
D002121:Calcium Channel Blockers; D002110:Caffeine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine