Characterization of T-type calcium current and its contribution to electrical activity in rabbit urethra.

Bradley, Eamonn and Anderson, U.A. and Woolsey, Siobhan M. and Thornbury, Keith D. and McHale, Noel G. and Hollywood, Mark A. (2004) Characterization of T-type calcium current and its contribution to electrical activity in rabbit urethra. Am J Physiol Cell Physiol., 286 (5). pp. 1078-1088.

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Abstract

Rabbit urethral smooth muscle cells were studied at 37 degrees C by using the amphotericin B perforated-patch configuration of the patch-clamp technique, using Cs(+)-rich pipette solutions. Two components of current, with electrophysiological and pharmacological properties typical of T- and L-type Ca(2+) currents, were recorded. Fitting steady-state inactivation curves for the L current with a Boltzmann equation yielded a V(1/2) of -41 +/- 3 mV. In contrast, the T current inactivated with a V(1/2) of -76 +/- 2 mV. The L currents were reduced by nifedipine (IC(50) = 225 +/- 84 nM), Ni(2+) (IC(50) = 324 +/- 74 microM), and mibefradil (IC(50) = 2.6 +/- 1.1 microM) but were enhanced when external Ca(2+) was substituted with Ba(2+). The T current was little affected by nifedipine at concentrations <300 nM but was increased in amplitude when external Ca(2+) was substituted with Ba(2+). Both Ni(2+) and mibefradil reduced the T current with an IC(50) = 7 +/- 1 microM and approximately 40 nM, respectively. Spontaneous electrical activity recorded with intracellular electrodes from strips of rabbit urethra consisted of complexes comprising a series of spikes superimposed on a slow spontaneous depolarization (SD). Inhibition of T current reduced the frequency of these SDs but had no effect on either the number of spikes per complex or the amplitude of the spikes. In contrast, application of nifedipine failed to significantly alter the frequency of the SD but reduced the number and amplitude of the spikes in each complex.

Item Type:	Article
Uncontrolled Keywords:	Action Potentials/drug effects; Animals; Barium/pharmacology; Calcium Channel Blockers/pharmacology; Calcium Channels, L-Type/drug effects; Calcium Channels, L-Type/physiology; Calcium Channels, T-Type/drug effects; Calcium Channels, T-Type/physiology; Electric Conductivity; Female; Male; Mibefradil/pharmacology; Models, Biological; Nickel/pharmacology; Nifedipine/pharmacology; Patch-Clamp Techniques; Rabbits; Urethra/metabolism; Urethra/physiology
Subjects:	Science
Research Centres:	Smooth Muscle Research Centre
Depositing User:	Concepta Woods
Date Deposited:	07 Mar 2012 10:24
Last Modified:	11 Nov 2014 16:10
URI:	https://eprints.dkit.ie/id/eprint/191

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