Journal of Pharmacological Sciences (Jan 2003)
Elecropharmacology of Taurine on the Hyperpolarization-Activated Inward Current and the Sustained Inward Current in Spontaneously Beating Rat Sino-Atrial Nodal Cells
Abstract
Modulation by taurine of the pacemaking activity and the underlying ionic currents, especially a hyperpolarization-activated inward current (If) and a sustained inward current (IST), 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 If. Application of taurine depressed more strongly the spontaneous activity at higher pCa levels. At all pCa levels, however, taurine (20 mM) increased the If 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 (IST) 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 Ca2+ current (ICaL) by 35.8 ± 2.5% (n = 8, P<0.01), whereas taurine enhanced the T-type Ca2+ current (ICaT) 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 (IKr) by 55.6 ± 3.3% (n = 6, P<0.001), but not the slowly activated K+ current (IKs). 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 ICaL, IKr and IST, and suggest that the If and ICaT currents make a minor contribution to pacemaking activity in rat SA nodal cells.