Effects of K+ channel openers on I-K(ATP) of human atrial myocytes at physiological temperatures

Citation
B. Pelzmann et al., Effects of K+ channel openers on I-K(ATP) of human atrial myocytes at physiological temperatures, N-S ARCH PH, 363(2), 2001, pp. 125-132
Citations number
39
Categorie Soggetti
Pharmacology & Toxicology
Journal title
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
ISSN journal
00281298 → ACNP
Volume
363
Issue
2
Year of publication
2001
Pages
125 - 132
Database
ISI
SICI code
0028-1298(200102)363:2<125:EOKCOO>2.0.ZU;2-O
Abstract
The aim of this study was to investigate the effects of the potassium chann el openers (PCOs) cromakalim and pinacidil on the ATP-dependent potassium c urrent I-K(ATP) in human atrial myocytes. Cells were isolated from the righ t atrial appendage obtained during cardiac surgery. Membrane currents were studied with the patch-clamp technique in the whole-cell recording mode at 36 degrees -37 degreesC. Under physiological conditions (4.3 mmol/l ATP in the pipette solution, ATP(i)) I-K(ATP) did not contribute to basal electric al activity. When ATP, was omitted from the pipette solution I-K(ATP) activ ated with a time lag of 4.92+/- 0.92 min (n=6) and was completely inhibited by glibenclamide. Using 4.3 mmol/l ATP(i) I-K(ATP) at +30 mV was in crease d by 2.04+/-0.51, 7.24+/-1.65 and 13.22+/-3.71 pA/pF (n=7) with 10, 30 and 100 mu mol/l cromakalim, respectively, and by 3.24+/-0.98 (n=6), 4.07+/-0.4 8 (n=10) and 3.46+/-1.23 pA/pF (n=6) with 10, 30 and 100 mu mol/l pinacidil , respectively. Control current density was 5.39+/-0.47 pA/pF (n=39). Using 1 mmol/l ATP(i) I-K(ATP) showed a more pronounced activation (4.81+/-3.28, n=6; 9.78+/-2.60, n=7; and 15.1+/-4.18 pA/pF n=6; with 10, 30 and 100 mu m ol/l pinacidil, respectively). I-K(ATP) activated by both compounds could b e effectively inhibited by glibenclamide. Repetitive exposure to pinacidil (30 mu mol/l at 4.3 mmol/l ATP(i) caused a potentiation of I-K(ATP) Current density at +30 mV was increased by 87% during the first and by 401% during the second pinacidil application (n=5). The data presented in this paper p rovide new information about electrophysiological characteristics of human atrial I-K(ATP) and its modulation by the PCOs cromakalim and pinacidil and suggest species-dependent differences.