Variance analysis of current fluctuations of adenosine- and baclofen-activated GIRK channels in dissociated neocortical pyramidal cells

Whole cell recordings were obtained from pyramidal cell somata acutely isol ated fi:om rat neocortex. In voltage-clamp mode, adenosine (0.3-1000 mu M), and the GABA(B) receptor agonist, baclofen (1-300 mu M), induced K+ curren t responses mediated by G protein-activated inwardly rectifying K+ (GIRK) c hannels. In our preparation, adenosine activated GIRK currents with an aver age EC50 of 2 mu M. Baclofen had an average EC50 of 26 mu M. To estimate an d compare unitary conductance and density of GIRK channels activated by eit her adenosine or baclofen, we performed variance analysis of current fluctu ations associated with the application of the two agonists at increasing co ncentrations. Irrespective of the agonist tested, GIRK channels displayed a n average single-channel conductance of 25 pS at our recording conditions ( [K+](o): 60 mM). Assuming that GIRK channel conductance increases in propor tion to the square root of [K+](o), this would translate into 5-6 pS at phy siological ion gradients. GIRK channels activated by adenosine or baclofen were not only identical in terms of unitary conductance, they also displaye d the same average density of 0.5 channels mu m(-2) for both agonists. Our data strongly suggest that the two compounds recruit the same type of chann el and thus most likely share a common transduction and effector system.