ATP and beta-adrenergic stimulation enhance voltage-gated K current inactivation in brown adipocytes

Sympathetic activation of brown fat thermogenesis stimulates adrenergic and purinergic receptors. We examined the effects of extracellular ATP and bet a -adrenergic agonists on voltage-activated K currents (IKv) in voltage-cla mped rat brown adipocytes. ATP or the beta -adrenergic agonist isoprotereno l increased the development of IKv inactivation during depolarizing voltage steps in perforated patch-clamped cells. The effects on inactivation devel oped slowly in the presence of agonist and continued to increase for long t imes following agonist washout. 8-bromo-cAMP or forskolin had similar effec ts on IKv inactivation. Development of IKv inactivation during depolarizati ons was consistently enhanced by ATP or beta -adrenergic stimulation in per forated-patch voltage-clamped cells but was not altered by these agents in whole cell recordings, suggesting that cytosolic factors are necessary for inactivation modulation. In either recording configuration, ATP or isoprote renol shifted the activation voltage dependence of IKv to more negative pot entials, indicating the activation effect is mediated by a different pathwa y. Since both P2 purinergic and beta -adrenergic signaling pathways generat e fatty acids, we tested whether fatty acids could reproduce these modulati ons of IKv. Linoleic or arachidonic acid applied in whole cell recordings h ad effects similar to those of ATP or isoproterenol in perforated-patch exp eriments. These results are consistent with the possibility that beta -adre nergic and P2 receptor stimulation modulate IKv through generation of fatty acids.