ACTIVATION OF MUSCARINIC K+ CHANNELS BY EXTRACELLULAR ATP AND UTP IN RAT ATRIAL MYOCYTES

The effects of extracellular adenine and pyrimidine nucleotides on the acetylcholine-activated K+ channels (K-ACh) in rat cardiac myocytes w ere compared and examined by using the patch-clamp technique. In perfo rated-patch whole-cell recording experiments, extracellular adenosine triphosphate (ATP) reversibly caused an increase in K+ current. 8-Cycl opentyl-1,3-dipropylxanthine (CPX; 1 mu M), a potent Ai-adenosine-rece ptor antagonist, only partially antagonized the ATP-induced increase i n K+ current, whereas glibenclamide (30 mu M) had no effect. In cell-a ttached mode, adenosine and ATP activated single channels that had nea rly identical conductance (29 pS) and open time (1.53 ms). These resul ts suggest that adenosine and ATP can activate the same population of K+ channels. Uridine triphosphate (UTP; 100 mu M) also caused an incre ase in steady-state K+ current. In cell-attached mode, the addition of UTP to the recording pipette solution (not in the bath solution) acti vated the channel current. The single-channel conductance and open tim e for UTP-induced channel current were 27 pS and 1.57 ms, respectively . These values were similar to those for the K+ channels activated by adenosine or ATP. The rank order of potency for the activation of K-AC h channels was adenosine = ATP > UTP. The addition of CPX (1 mu M) to the pipette solution attenuated the ATP-induced channel activity by si milar to 70% and fully prevented activation by AMPCPP, a less hydrolyz able ATP analog but did not cause any effect on UTP-induced channel ac tivity. In pertussis toxin-treated cardiac myocytes, no any activity o f UTP-induced K-ACh-channel current was observed. Our results demonstr ate that extracellular ATP and UTP can directly activate K-ACh-channel current. This activation also was linked to pertussis toxin-sensitive G protein. The effect of extracellular ATP is mainly caused by the ac tion on binding to Al-adenosine receptor, whereas the effect of extrac ellular UTP may be mediated possibly by P-2U-purinergic (or 5'-nucleot ide) receptor.