[Ca2+]i-dependent actions of taurine in spontaneously beating rabbit sino-atrial nodal cells.
Modulation by taurine of the pacemaking activity and the underlying ionic currents in rabbit sino-atrial nodal cells was investigated at low and high cellular Ca2+ concentrations ([Ca2+]i) using a patch-clamp technique. At both pCa 8 and 6, taurine depressed the spontaneous activity, more strongly at pCa 6 than at pCa 8. Taurine, 20 mM, markedly inhibited the L-type Ca2+ current: by 56.9+/-2.8% (n=6, P<0.001) at pCa 8, and by 97.6+/-3.8% (n=7, P<0.001) at pCa 6. Also at 20 mM, taurine decreased the delayed rectifier K+ current by 26.8+/-2.6% (n=6, P<0.01) at pCa 6, whereas taurine had less or no effect at pCa 8. The hyperpolarization-activated inward current also decreased at both pCa 8 and 6, by 18.3+/-1.3% (n=8, P<0.05) and by 20.8+/-3.3% (n=8, P<0.05) in 20 mM taurine, respectively. Taurine caused a more potent inhibitory effect at pCa 6. Taurine often elicited dysrhythmias, at 20 mM, in 3 of 17 cells at pCa 8 and in 12 of 16 cells at pCa 6. During washout, the incidence of dysrhythmias or arrest increased further. These results indicate that taurine exerts more potent inhibitory actions on ionic currents under Ca2+ overload conditions in rabbit sino-atrial nodal cells. However, taurine would possibly elicit a cellular Ca2+ overload, when taurine application was discontinued.
Satoh
H
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Department of Pharmacology, Division of Molecular and Cellular Biology, Nara Medical University, Nara 634-8521, Kashihara, Japan. hysat@naramed-u.ac.jp
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects; D010138:Pacemaker, Artificial; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013654:Taurine / Q000494:pharmacology*
D020746:Calcium Channels, L-Type; D015221:Potassium Channels; D013654:Taurine; D002118:Calcium