Effect of verapamil on the non-adrenergic response of the field stimulated rat vas deferens

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Abstract
A comparison has been made, in the present study, between the effects of verapamil (reported to have smooth muscle depolarizing action) and K+ depolarization on the responses of noradrenaline, ATP and those of field stimulation on the vas deferens obtained from reserpinized rats. Field stimulation of the vas using single pulse (1 ms pulse width; supramaximal voltage) resulted in a fast twitch response reaching a maximum at 300±20 ms. Verapamil (6×10−6 M) significantly potentiated this response. Verapamil potentiated the twitch component of the biphasic response resulting from field stimulation of the intrinsic nerves with repetitive pulses, while the tonic component was markedly inhibited. Verapamil enhanced the ATP (7×10−5 M) response, while the phasic and tonic components of KCl (5.36×10−2 M)-induced biphasic responses were nearly abolished. While the phasic component of the noradrenaline (7×10−6 M) response remained unaltered in the presence of verapamil, the tonic component was markedly inhibited and rhythmicity following phasic component was markedly enhanced. Partial depolarization, achieved by increasing K+ concentration in the normal Krebs by two-fold i.e., to 11.8 mM, enhanced the responses of ATP, nor-adrenaline and the twitch resulted from the single pulse stimulation. The finding that verapamil potentiates the contractile response to exogenously applied ATP, which is believed to be the “noradrenergic” neurotransmitter in the vas deferens, suggests that this is the mechanism through which verapamil potentiates the twitch responses to field stimulation of the nerve supply. The differential effects of verapamil and depolarizing Kreb's solution on the responses to noradrenaline do not explain the smooth muscle depolarization as a possible mechanism in the enhancement of the responses of ATP and those of motor nerve stimulation. The results of the present study with verapamil show that the tonic responses, obtained with various stimulants in rat vas, results from the influx of Ca2+ through voltagedependent ion channels which are normally sensitive to calcium channel blockers. The observations made in the present study along with the reports available from the literature support the hypothesis that ATP might be a transmitter mediating the nonadrenergic response in the rat vas deferens and being released along with noradrenaline to electrical field stimulation of the motor nerves.