Blockade of the ATP-sensitive Potassium Channel by Taurine in Rabbit Ventricular Myocytes

Abstract

Using patch-clamp techniques, the effects of taurine on properties of ATP-sensitive K +(K ATP) channel of rabbit ventricular myocytes were examined. Intracellular taurine (20 m m) markedly depressed the K ATPchannel activity. The taurine concentration for half-inhibition (apparent K d) was 13.5 m mwith a Hill coefficient, n, of 1.3. Intracellular taurine caused channel inhibition without affecting channel inhibition by ATP. In control conditions, the ATP concentration for half-inhibition (K i) and n were 73 μ mand 1.2 ( n=6), respectively. In the presence of taurine, K iand n were 81 μ mand 1.3 ( n=6), respectively. Analysis of the open and closed time distributions showed that taurine decreased the life time of bursts and increased the inter-burst interval and/or reduced the number of functional channels. 2,4-Dinitrophenol (DNP) activated K ATPchannel after a lag period. This lag period was much longer after pretreatment with taurine (6.6±1.2 min, n=5) than in the absence of taurine (2.8±1.5 min, n=12). When DNP was removed in the bath solution, channel activity showed a gradual reduction with time and this process was facilitated by the presence of external taurine (20 m m). From these results it is suggested that taurine blocks K ATPchannel activity in dose-dependent manner and the depletion of taurine during myocardial ischemia contribute to the early activation of the K ATPchannel.