Elecropharmacology of taurine on the hyperpolarization-activated inward current and the sustained inward current in spontaneously beating rat sino-atrial nodal cells.
Modulation by taurine of the pacemaking activity and the underlying ionic currents, especially a hyperpolarization-activated inward current (I(f)) and a sustained inward current (I(ST)), in rat sino-atrial (SA) nodal cells was investigated at different pCa levels using a patch-clamp technique. Increasing pCa levels from 10 to 6 stimulated the spontaneous activity and simultaneously increased the I(f). Application of taurine depressed more strongly the spontaneous activity at higher pCa levels. At all pCa levels, however, taurine (20 mM) increased the I(f) by 60.1 +/- 1.7% (n = 8, P<0.001) at pCa 10 and by 48.0 +/- 1.4% (n = 8, P<0.01) at pCa 7. At pCa 7, taurine (10 and 20 mM) decreased the sustained inward current (I(ST)) by 13.3 +/- 1.1% (n = 5, P<0.05) and by 38.1 +/- 2.4% (n = 5, P<0.01), respectively. Taurine (20 mM) inhibited the L-type Ca(2+) current (I(CaL)) by 35.8 +/- 2.5% (n = 8, P<0.01), whereas taurine enhanced the T-type Ca(2+) current (I(CaT)) by 29.3 +/- 2.9% (n = 8, P<0.05). Also, taurine at pCa 7 decreased the delayed rectifier K(+) current; taurine at 20 mM inhibited the rapidly activated K(+) current (I(Kr)) by 55.6 +/- 3.3% (n = 6, P<0.001), but not the slowly activated K(+) current (I(Ks)). Taurine often elicited dysrhythmias, dependent on taurine's concentrations and pCa levels. These results indicate that taurine causes a negative chronotropic effect due to the inhibitions of the pacemaking ionic currents such as I(CaL), I(Kr) and I(ST), and suggest that the I(f) and I(CaT) currents make a minor contribution to pacemaking activity in rat SA nodal cells.
Satoh
Hiroyasu
H
Department of Pharmacology, Division of Molecular and Cellular Biology, Nara Medical University, Japan. hysat@naramed-u.ac.jp
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013654:Taurine / Q000494:pharmacology*
D015220:Calcium Channels; D007473:Ion Channels; D015221:Potassium Channels; D013654:Taurine