Expression of heart K+ channels in adrenalectomized and catecholamine-depleted reserpine-treated rats

We studied cardiac outward K currents (transient and sustained) by the whole-cell patch-clamp technique and the Kv4.2, Kv4.3, Kv1.4, Kv1.5, Kv1.2 and Kv2.1 expression of voltage-gated K channel by RT-PCR, in ventricular myocytes from two models of catecholamine-depleted adult rats. We induced endogenous catecholamine depletion by reserpine treatment and used adrenalectomized rats as a model of plasma catecholamine depletion. In reserpine-treated rats (97% decrease in endogenous norepinephrine content of the heart), the amplitude of the transient outward current was decreased by 48% and Kv4.2 and Kv4.3 mRNA levels were decreased by 57% and 34%, respectively. The amount of Kv1.5 mRNA tripled, with no change in sustained current density. This increase was not confirmed by immunostaining for the Kv1.5 protein. The amplitude of K currents and their corresponding mRNA levels returned to control values following recovery from reserpine treatment. In contrast, in adrenalectomized rats (98% decrease in plasma epinephrine concentration), we observed no change in the amplitude of outward K currents or in Kv mRNA levels. These results suggested a role for sympathetic innervation and endogenous norepinephrine in the regulation of transcription of cardiac outward K currents in physiological and pathological situations.