BaCl₂‐ and 4‐aminopyridine‐evoked phasic contractions in the rat vas deferens

The actions of BaCl₂ and 4‐aminopyridine, blockers of K⁺ channels, on the mechanical activity of the epididymal half of the rat vas deferens were investigated. Both BaCl₂ and 4‐aminopyridine dose‐dependently evoked phasic contractions. High extracellular potassium (35–40 mM) caused a tonic contraction but abolished the BaCl₂‐ and 4‐aminopyridine‐induced phasic activity and reduced the BaCl₂‐induced sustained component of contraction, but increased the 4‐aminopyridine‐induced tonic contraction. Omission of calcium from the extracellular medium totally abolished the 4‐aminopyridine‐induced response but only reduced the mean amplitude of phasic contractions induced by BaCl. Procaine (10 mM), an inhibitor of internal calcium release, completely abolished the phasic activity and reduced the sustained contraction induced by BaCl₂. The remaining tone was abolished by nifedipine (1 μm). Tetraethylammonium (1 mM) suppressed the amplitude of the BaCl₂‐induced phasic contractions, and induced a biphasic increase in tonic tension. The BaCl₂‐induced responses were resistant to prazosin (1 μm), yohimbine (3 μm), propranolol (3 μm) or atropine (3 μm); in contrast, the 4‐aminopyridine‐induced activity was effectively inhibited by prazosin (Éμm) attenuated by yohimbine (Éμm) and atropine (Éμm) but not by propranolol (3μm). The 4‐aminopyridine‐induced response was abolished by pretreatment of the vas deferens with 6‐hydroxydopamine (0.5 mM). The results indicate that the BaCl₂‐evoked activity in the vas deferens was mainly due to blockade of Ba²⁺‐sensitive K⁺ channels on the smooth muscle plasma membrane. Subsequent calcium entry through the depolarized plasma membrane was needed to trigger generation of phasic contractions. 4‐Aminopyridine‐induced action, however, was largely mediated by neurotransmitters released from the depolarized nerve terminals as a result of blockade of K⁺ channels. 1995 British Pharmacological Society