The action of isoproterenol and BAY K 8644 on the potential-dependent Ca2currents in isolated ground squirrel cardiac myocytes was studied in two st
ates of the animal (active and hibernating). It was shown that in cardiac m
iocytes of active animals the effect of both drugs depends on the holding p
otential V-h. At holding potentials of about -50 mV, both isoproterenol and
BAY K 8644 increase the Ca2+ current and their action is additive. At hold
ing potentials of about -20 mV, both drugs inhibit the Ca2+ current. In car
diac myocytes from hibernating animals, isoproterenol increases Ca2+ curren
t at any holding potentials, while the effect of BAY K 8644 does not differ
significantly from its effect on active animals. The joint action of the t
wo drugs causes the inhibition of the Ca2+ current at high holding potentia
ls. In terms of the two-site Ca2+ channel model, this means that one of the
two pathways of channel phosphorylation is blocked in hibernating animal c
ardiac cells, and BAY K 8644 restores this pathway.