Norepinephrine-induced sustained inward current in brown fat cells: a1-mediated by nonselective cation channels

Koivisto, Ari, Detlef Siemen, and Jan Nedergaard. Norepinephrine-induced sustained inward current in brown fat cells: a1-mediated by nonselective cation channels. Am J Physiol Endocrinol Metab 279: E963–E977, 2000.—The nature of the sustained norepinephrine-induced depolarization in brown fat cells was examined by patch-clamp techniques. Norepinephrine (NE) stimulation led to a whole cell current response consisting of two phases: a first inward current, lasting for only 1 min, and a sustained inward current, lasting as long as the adrenergic stimulation was maintained. The nature of the sustained current was here investigated. It could be induced by the a1-agonist cirazoline but not by the b3-agonist CGP-12177A. Reduction of extracellular Cl concentration had no effect, but omission of extracellular Ca or Na totally eliminated it. When unstimulated cells were studied in the cell-attached mode, some activity of '30 pS nonselective cation channels was observed. NE perfusion led to a 10-fold increase in their open probability (from '0.002 to '0.017), which persisted as long as the perfusion was maintained. The activation was much stronger with the a1-agonist phenylephrine than with the b3-agonist CGP12177A, and with the Ca ionophore A-23187 than with the adenylyl cyclase activator forskolin. We conclude that the sustained inward current was due to activation of '30 pS nonselective cation channels via a1-adrenergic receptors and that the effect may be mediated via an increase in intracellular free Ca concentration.