Cromakalim (BRL 34915) restores in vitro the membrane potential of depolarized human skeletal muscle fibres

The purpose of the present study was to analyze the effects of
cromakalim (BRL 34915), a potent drug from a new class of drugs
characterized as K+ channel openers, on the electrical activity of
human skeletal muscle. Therefore, intracellular recordings were
used to measure the effects of cromakalim on the membrane potential
and input conductance of fibres from human skeletal muscle
biopsies. Cromakalim in a concentration above 1 mol/l induced an
increase in membrane K+ conductance. This effect resulted in a
membrane hyperpolarization. The magnitude of this polarization
depended on the difference between resting and K+ equilibrium
potential. The effect had a rapid onset and was quickly reversible
after washing. Fibres from two patients with hyperkalaemic periodic
paralysis showed an excessive membrane depolarization during and
also after exposure to an slightly elevated extracellular K+
concentration. In the latter situation, cromakalim repolarized the
fibres to the normal resting potential. Tolbutamide (1 mmol/l) and
Ba2+ (3 mmol/l) strongly antagonized the effect of cromakalim. The
data show that cromakalim hyperpolarizes depolarized human skeletal
muscle fibres maintained in vitro. The underlying mechanism is
probably an activation of otherwise silent, ATP-regulated K+
channels. Such an effect may be of therapeutic benefit in a
situation in which a membrane depolarization causes muscle
paralysis.