Role of the T-type Ca2+ current on the contractile performance of guinea pig detrusor smooth muscle

Aims: The importance of the T-type Ca(2+) current in determining detrusor contractile function was investigated by using guinea pig muscle in vitro. Methods: NiCl(2) (200 muM) was used to block selectively the T-type Ca(2+) current, and 20 muM verapamil was used to block the L-type Ca(2+) current in this tissue. The selectivity of these agents at such concentrations has been previously demonstrated. Results: In normal extracellular solution (4 mM KCl) 200 muM NiCl(2) and 20 muM verapamil reduced electrically stimulated contractions by 17 +/- 6% and 65 +/- 10%, respectively. At high concentrations of the two agents, the contraction was completely abolished by NiCl(2), but by only 74 +/- 18% in the case of verapamil; this finding suggests that NiCl(2) has additional negative inotropic actions at higher concentrations. Carbachol and KCl contractures were attenuated to a similar extent to that of electrically stimulated contractions by NiCl(2) and verapamil, which suggests that they act on the muscle rather than the motor nerve. The dependence of the membrane potential on the relative ability of NiCl(2) and verapamil to attenuate the contraction was tested by varying the extracellular [KCl], [KCl](o). Varying [KCl](o) between 2 and 10 mM depolarised detrusor myocytes from (-65.1 +/- 4.7 mV to -42.7 +/- 4.0 mV (a slope of 32 mV per 10-fold change of [KCl](o)). In low [KCl](o), blockade by NiCl(2) was more effective and that of verapamil less effective; at high [KCl](o), the reverse potency was recorded. Conclusions: The data are consistent with the hypothesis that Ca(2+) influx through both T-type and L-type Ca(2+) channels determines the contractile status of detrusor smooth muscle and that T-type channel activity is more important at membrane potentials near the resting level. A significant role for T-type channel activity in the resting state was evident in that spontaneous contractions were attenuated to a greater extent than evoked contractions. (C) 2003 Wiley-Liss, Inc.