calcimycin and cirazoline

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 alpha(1)-agonist cirazoline but not by the beta(3)-agonist CGP-12177A. Reduction of extracellular Cl(-) concentration had no effect, but omission of extracellular Ca(2+) or Na(+) totally eliminated it. When unstimulated cells were studied in the cell-attached mode, some activity of approximately 30 pS nonselective cation channels was observed. NE perfusion led to a 10-fold increase in their open probability (from approximately 0.002 to approximately 0.017), which persisted as long as the perfusion was maintained. The activation was much stronger with the alpha(1)-agonist phenylephrine than with the beta(3)-agonist CGP-12177A, and with the Ca(2+) ionophore A-23187 than with the adenylyl cyclase activator forskolin. We conclude that the sustained inward current was due to activation of approximately 30 pS nonselective cation channels via alpha(1)-adrenergic receptors and that the effect may be mediated via an increase in intracellular free Ca(2+) concentration.

Topics: Adenylyl Cyclases; Adipose Tissue, Brown; Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Animals; Calcimycin; Calcium; Cations; Chlorides; Colforsin; Electric Conductivity; Enzyme Activation; Extracellular Space; Imidazoles; Ion Channels; Ionophores; Male; Norepinephrine; Patch-Clamp Techniques; Phenylephrine; Propanolamines; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, alpha-1; Sodium