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
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.