Effects of cromakalim (BRL 34915) on potassium conductances in CA3 neurons of the guinea-pig hippocampus in vitro

The action of the potassium channel activator, cromakalim (BRL
34915), on membrane potential, input resistance and
current-voltage-relationship of CA3 neurons in a slice preparation
of the guinea-pig hippocampus was investigated by means of
intracellular recordings. In the presence of tetrodotoxin,
cromakalim (30–100 mol/l) produced a hyperpolarization up to 4 mV
associated with a decrease in input resistance up to 10 MOhms.
Determination of the equilibrium potential of the cromakalim action
revealed that the hyperpolarization is due to the activation of a
potassium conductance. This cromakalim-activated potassium
conductance was voltage-dependent, i.e. it increased with
hyperpolarization. Among a number of potassium channel blockers
tested, only Cs+ (2 mmol/l) and Ba2+ (0.5 mmol/1) were able to
inhibit the cromakalim-induced effects. Simultaneously, both
cations suppressed the hyperpolarizing inward rectification
(anomalous rectification) in these neurons, indicating that
cromakalim activated or potentiated an inwardly rectifying
potassium conductance. In addition, cromakalim slightly enhanced
both amplitude and duration of afterhyperpolarizations following
single calcium-dependent action potentials, suggesting that
cromakalim might have a weak facilitatory effect on
calcium-dependent potassium conductances.