ATP suppresses activity of Ca 2 -activated K channels by Ca2 chelation

Abstract:  ATP suppresses activity of Ca(2+)-activated K+ channels by Ca2+ chelation. Kl?ckner U, Isenberg G. Department of Physiology, University of Cologne, Federal Republic of Germany. Ca(2+)-act ivated maxi K+ channels were studied in inside-out patches from smooth muscle cells isolated from either porcine coronary arteries or guinea-pig urinary bladder. As described by Groschner et al. (Pf?gers Arch 417:517, 1990), channel activity (NPo) was stimulated by 3 microM [Ca2+]c (1 mM Ca-EGTA adjusted to a calculated pCa of 5.5) and was suppressed by the addition of 1 mM Na2ATP. The following results suggest that suppression of NPo by Na2ATP is due to Ca2+ chelation and hence reduction of [Ca2+]c and reduced Ca2+ activation of the channel. The effect was absent when Mg ATP was used instead of Na2ATP. The effect was diminished by increasing the [EGTA] from 1 to 10 mM. The effect was absent when [Ca2+]c was buffered with 10 mM HDTA (apparent pKCa 5.58) instead of EGTA (pKCa 6.8). A Ca(2+)-sensitive electrode system indicated that 1 mM Na2ATP reduced [Ca2+]c in 1 mM Ca-EGTA from 3 microM to 1.4 microM. Na2ATP, Na2GTP, Li4AMP-PNP and NaADP reduced measured [Ca2+]c in parallel with their suppression of NPo. After the Na2ATP-induced reduction of [Ca2+]c was re-adjusted by adding either CaCl2 or MgCl2, the effect of Na2ATP on NPo disappeared. In vivo, intracellular [Mg2+] exceeds free [ATP4-], hence ATP modulation of maxi K+ channels due to Ca2+ chelation is without biological relevance. PMID: 1553255 [PubMed - indexed for MEDLINE]