The effects of extracellular adenine and pyrimidine nucleotides on the acetylcholine-activated K+ channels (K(Ach)) in rat cardiac myocytes were compared and examined by using the patch-clamp technique. In perforated- patch whole-cell recording experiments, extracellular adenosine triphosphate (ATP) reversibly caused an increase in K+ current. 8-Cyclopentyl-1,3- dipropylxanthine (CPX; 1 μM), a potent A1-adenosine-receptor antagonist, only partially antagonized the ATP-induced increase in K+ current, whereas glibenclamide (30 μM) had no effect. In cell-attached mode, adenosine and ATP activated single channels that had nearly identical conductance (29 pS) and open time (1.53 ms). These results suggest that adenosine and ATP can activate the same population of K+ channels. Uridine triphosphate (UTP; 100 μM) also caused an increase in steady-state K+ current. In cell-attached mode, the addition of UTP to the recording pipette solution (not in the bath solution) activated the channel current. The single-channel conductance and open time 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(ACh) channels was adenosine = ATP > UTP. The addition of CPX (1 μM) to the pipette solution attenuated the ATP-induced channel activity by ~70% and fully prevented activation by AMPCPP, a less hydrolyzable ATP analog but did not cause any effect on UTP-induced channel activity. In pertussis toxin- treated cardiac myocytes, no any activity of UTP-induced K(ACh)-channel current was observed. Our results demonstrate 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 action on binding to A1-adenosine receptor, whereas the effect of extracellular UTP may be mediated possibly by P(2U)-purinergic (or 5'-nucleotide) receptor.
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine