Specific dihydropyridines may affect gating properties of certain subsets of adenosin-triphosphate-dependent K-channels in myocardial tissue and hence modulate its response to ischaemia

Journal of Clinical and Basic Cardiology 2000; 3 (2): 133-134

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Keywords: Dihydropyridin,  KATP-Kanal,  myokardiale Ischämie,  dihydropyridine,  KATP-channels,  myocardial ischaemia

It has been shown that dihydropyridines exert a cardio-protective effect during experimental ischaemia. This effect is reflected in a reduced K-efflux from the ischaemic tissue. Recently we have shown that ischaemic K-efflux is largely mediated by ATP-dependent potassium channels. Using K-selective microelectrodes we studied the effect of nisoldipine on K-efflux during simulated ischaemia. While ischaemic K-efflux was Ca-dependent in stimulated preparations, surface K (Ko) after 3 minutes of simulated ischaemia at one Hertz in the presence of 2.5 and 0 mM Ca was 7.0 ± 0.1 and 6.6 ± 0.1 mM respectively (n = 5), it was independent of extracellular Ca in resting preparations. After 3 minutes of simulated ischaemia at rest in the presence of 2.5 and 0 mM Calcium Ko rose by 2.1 ± 0.0 and 2.1 ± 0.0 respectively (n = 5) in the same preparation. In contrast, 10-5 mM nisoldipine inhibited ischaemic K-efflux both in stimulated and resting preparations (Ko rose from 4.5 mM to 7.1 ± 0.1 mM within 3 minutes of simulated ischaemia; n = 5, ± SEM, field stimulation 1 Hz), whereas in the presence of 10-5 mM nisoldipine the same preparation showed a Ko of 6.0 ± 0.2 after 3 minutes of simulated ischaemia. Ko after 3 minutes of simulated ischaemia in resting preparations without nisoldipine was 6.7 ± 0.1 and 5.5 ± 0.1 respectively (p < 0.0001). Our results show a cardioprotective action of nisoldipine during simulated ischaemia which leads to an inhibition of ischaemic K-efflux. We suggest a direct effect of nisoldipine on the KATP-channel. The latter is mainly responsible for ischaemic K-loss. J Clin Basic Cardiol 2000; 3: 133-4.