Actions of taurine on the L-type Ca2+ channel current in guinea pig ventricular cardiomyocytes.
Effects of taurine on the L-type channel in isolated guinea pig ventricular cardiomyocytes were examined at different Ca2+ concentrations by using whole-cell and cell-attached voltage-clamp modes. All experiments were performed at 36 degrees C. In whole-cell voltage-clamp experiments, test pulses were applied between -20 to +60 mV from a holding potential of -40 mV. When [Ca]i was pCa 6, addition of 10 and 20 mM taurine to the bath solution reduced the Ca2+ current (I(Ca)) at 0 mV by 14.4 +/- 2.0% (n = 8; p < 0.01) and 31.5 +/- 2.2% (n = 8; p < 0.001), respectively. In contrast, when [Ca]i was pCa 8, I(Ca) at +10 mV was enhanced by 10.1 +/- 2.2% (n = 7; p < 0.05) at 10 mM taurine and by 41.7 +/- 2.1% (n = 7; p < 0.001) at 20 mM taurine. Taurine increased the time constants (tau(f) and tau(s)) of inactivation phase for I(Ca) current at both pCa 8 and 6. In cell-attached voltage-clamp experiments, taurine (20 mM) decreased the open probability of unitary Ba2+ current from 0.63 +/- 0.06 to 0.39 +/- 0.09 (n = 5; p < 0.01) at 5.4 mM [Ca]o, whereas taurine increased it from 0.21 +/- 0.04 to 0.48 +/- 0.07 (n = 4; p < 0.01) at 0.9 mM [Ca]o. Taurine did not affect the channel conductance. In addition, taurine (20 mM) increased the time constants (tau(of) and tau(os)) of the open time and decreased tau(cs) of the closed time at 0.9 mM [Ca]o. At 5.4 mM [Ca]o, the tau(os) and tau(cs) were also increased and decreased, respectively. tau(of) and tau(cf) were unaffected. These results indicate that taurine modulates the open probability of L-type Ca2+ channel dependent on [Ca]i and [Ca]o, thereby maintaining the normal [Ca]i level.
Satoh
H
H
Department of Pharmacology, Nara Medical University, Kashihara, Japan.
Horie
M
M
D000818:Animals; D001464:Barium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006352:Heart Ventricles / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009206:Myocardium / Q000166:cytology; D018408:Patch-Clamp Techniques; D013654:Taurine / Q000494:pharmacology*; D013997:Time Factors; D016276:Ventricular Function
D015220:Calcium Channels; D013654:Taurine; D001464:Barium