Acute simulated ischaemia produces both inhibition and activation of K+ currents in isolated ventricular myocytes.
OBJECTIVE
The aim was to investigate the effects of acute ischaemia on cardiac repolarizing K+ currents.


METHODS
We developed a model of acute ischaemia in isolated rat ventricular myocytes transiently surrounded with a mineral oil droplet. During ischaemic challenges, we recorded intracellular pH using the fluorescent probe seminaphthorhodafluor-1 (SNARF-1) and whole-cell K+ currents using the patch-clamp technique.


RESULTS
Decrease in intracellular pH (pH1) during simulated ischaemia was dependent upon the extracellular proton buffer used (pH1 decreased from 7.44 +/- 0.02 to 7.16 +/- 0.04 in a Hepes-buffered medium and from 7.08 +/- 0.04 to 6.56 +/- 0.07 with bicarbonate buffer). In Hepes, action potential duration initially lengthened and then shortened under the effects of ischaemia. Initial action potential duration lengthening was concomitant with a block of the inward rectifier K+ current, whereas late shortening corresponded with the activation of the ATP-sensitive K+ current. Similar changes occurred in bicarbonate buffer although with different amplitudes and kinetics. Patch-clamp experiments also showed inhibition of the transient outward K+ current. Brief transient episodes of ischaemia activated ATP-sensitive K+ current in only 20% of control cells (n = 21) but in 100% of cells treated with 15 microM cromakalim (n = 9).


CONCLUSIONS
(i) Simulated ischaemia produces complex effects on repolarizing K+ currents including both inhibition and activation; (ii) cromakalim accelerates activation of ATP-sensitive K+ current during simulated ischaemia.
Henry
P
P
Département de Cardiologie, Hôpital Broussats, Paris, France.
Popescu
A
A
Pucéat
M
M
Hinescu
M E
ME
Escande
D
D
D000200:Action Potentials; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D019806:Cromakalim; D006863:Hydrogen-Ion Concentration; D019157:Ischemic Preconditioning, Myocardial; D017202:Myocardial Ischemia / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism*
D001578:Benzopyrans; D015221:Potassium Channels; D011758:Pyrroles; D019806:Cromakalim; D000254:Sodium-Potassium-Exchanging ATPase