BLOCKADE OF THE ATP-SENSITIVE POTASSIUM CHANNEL BY TAURINE IN RABBIT VENTRICULAR MYOCYTES

Using patch-clamp techniques, the effects of taurine on properties of ATP-sensitive K+ (K-ATP) channel of rabbit ventricular myocytes were e xamined. Intracellular taurine (20 nM) markedly depressed the K-ATP ch annel activity, The taurine concentration for half-inhibition (apparen t K-d) was 13.5 mM with a Hill coefficient, n, of 1.3, Intracellular t aurine caused channel inhibition without affecting channel inhibition by ATP. In control conditions, the ATP concentration for half-inhibiti on (K-i) and n were 73 mu M and 1.2 (n=6), respectively. In the presen ce of taurine, K-i and n were 81 mu M and 1.3 (n=6), respectively. Ana lysis of the open and closed time distributions showed that taurine de creased 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-ATP channel after a lag period. This lag period was m uch 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 remov ed in the bath solution, channel activity showed a gradual reduction w ith time and this process was facilitated by the presence of external taurine (20 mM). From these results it is suggested that taurine block s K(ATP) channel activity in dose-dependent manner and the depletion o f taurine during myocardial ischemia contribute to the early activatio n of the K-ATP channel. (C) 1996 Academic Press Limited