Norepinephrine-induced sustained inward current in brown fat cells: alpha(1)-mediated by nonselective cation channels

The nature of the sustained norepinephrine-induced depolarization in brown fat cells was examined by patch-clamp techniques. Norepinephrine (NE) stimu lation led to a whole cell current response consisting of two phases: a fir st 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 al pha (1)-agonist cirazoline but not by the beta (3)-agonist CGP-12177A. Redu ction of extracellular Cl- concentration had no effect, but omission of ext racellular Ca2+ or Na+ totally eliminated it. When unstimulated cells were studied in the cell-attached mode, some activity of approximate to 30 pS no nselective cation channels was observed. NE perfusion led to a 10-fold incr ease in their open probability (from approximate to0.002 to approximate to0 .017), which persisted as long as the perfusion was maintained. The activat ion was much stronger with the alpha (1)-agonist phenylephrine than with th e beta (3)-agonist CGP-12177A, and with the Ca2+ ionophore A-23187 than wit h the adenylyl cyclase activator forskolin. We conclude that the sustained inward current was due to activation of approximate to 30 pS nonselective c ation channels via alpha1-adrenergic receptors and that the effect may be m ediated via an increase in intracellular free Ca2+ concentration.