Role of the T-type XXXX current on the contractile performance of @entity840 detrusor smooth muscle.

@entity4437 @entity1855 @entity840 @entity141 @entity5402 @entity4338
AIMS: The importance of the T-type @entity141 current in determining detrusor contractile function was investigated by using @entity840 muscle in vitro. METHODS: @entity4437 (200 microM) was used to block selectively the T-type @entity141 current, and 20 microM @entity1855 was used to block the L-type @entity141 current in this tissue. The selectivity of these agents at such concentrations has been previously demonstrated. RESULTS: In normal extracellular solution (4 mM @entity4338 ) 200 microM @entity4437 and 20 microM @entity1855 reduced electrically stimulated contractions by 17 +/- 6% and 65 +/- 10%, respectively. At high concentrations of the two agents, the contraction was completely abolished by @entity4437 but by only 74 +/- 18% in the case of @entity1855 ; this finding suggests that @entity4437 has additional negative inotropic actions at higher concentrations. @entity5402 and @entity4338 contractures were attenuated to a similar extent to that of electrically stimulated contractions by @entity4437 and @entity1855 , which suggests that they act on the muscle rather than the motor nerve. The dependence of the membrane potential on the relative ability of @entity4437 and @entity1855 to attenuate the contraction was tested by varying the extracellular @entity4338 , [ @entity4338 ](o). Varying [ @entity4338 ](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 [ @entity4338 ](o)). In low [ @entity4338 ](o),blockade by @entity4437 was more effective and that of @entity1855 less effective; at high [ @entity4338 ](o), the reverse potency was recorded. CONCLUSIONS: The data are consistent with the hypothesis that @entity141 influx through both T-type and L-type @entity141 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.
