Beta-adrenergic modulation of K+ current in human T lymphocytes.
The whole-cell voltage-clamp technique was employed to study the beta-adrenergic modulation of voltage-gated K+ currents in CD8+ human peripheral blood lymphocytes. The beta-receptor agonist, isoproterenol, decreased the peak current amplitude and increased the rate of inactivation of the delayed rectifier K+ current. In addition, isoproterenol decreased the voltage dependence of steady-state inactivation and shifted the steady-state inactivation curve to the left. Isoproterenol, on the other hand, had no significant effect on the steady-state parameters of current activation. The isoproterenol-induced decrease in peak current amplitude was inhibited by the beta-blocker propranolol. Bath application of dibutyryl cAMP (1 mM) mimicked the effects of isoproterenol on both K+ current amplitude and time course of inactivation. Furthermore, the reduction in the peak current amplitude in response to isoproterenol was attenuated when PKI5-24 (2-5 microM), a synthetic peptide inhibitor of cAMP-dependent protein kinase, was present in the pipette solution. The increase in the rate of inactivation of the K+ currents in response to isoproterenol was mimicked by the internal application of GTP-gamma-S (300 microM) and by exposure of the cell to cholera toxin (1 microgram/ml), suggesting the involvement of a G protein. These results demonstrate that the voltage-dependent K+ conductance in T lymphocytes can be modulated by beta-adrenergic stimulation. The effects of beta-agonists, i.e., isoproterenol, appear to be receptor mediated and could involve cAMP-dependent protein kinase as well as G proteins. Since inhibition of the delayed rectifier K+ current has been found to decrease the proliferative response in T lymphocytes, the beta-adrenergic modulation of K+ current may well serve as a feedback control mechanism limiting the extent of cellular proliferation.
Soliven
B
B
Department of Neurology, University of Chicago, Illinois 60637.
Nelson
D J
DJ
D000242:Cyclic AMP / Q000378:metabolism; D004553:Electric Conductivity; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology*; D007700:Kinetics; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
D015221:Potassium Channels; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol; D011188:Potassium