Developmental downregulation of ATP-sensitive potassium conductance in astrocytes in situ

In many neural and non-neural cells, ATP-sensitive potassium (K-ATP) channe ls couple the membrane potential to energy metabolism We investigated the a ctivation of K-ATP currents in astrocytes of different brain regions (hippo campus, cerebellum, dorsal vagal nucleus) by recording whole-cell currents with the patch-clamp technique in acute rat brain slices. Pharmacological t ools, hypoglycemia and specific compounds in the pipette solution (cAMP, UD P), were used to modulate putative K-ATP currents. The highest rate of K-AT P specific currents was observed with a pipette solution containing cAMP an d external stimulation with diazoxide (0.3 mM). The diazoxide-activated cur rent had a reversal potential negative to -80 mV and was inhibited by tolbu tamide (0.2 mM). We found that not all cells activated a K-ATP current, and that the portion of cells with functional K-ATP channel expression was dev elopmentally downregulated. Whereas diazoxide activated K-ATP currents in 5 7% of the astrocytes in rats aged 8-11 days (n = 21), the rate decreased to 38% at 12-15 days (n = 29) and to 8% at 16-19 days (n = 12). No significan t difference was observed for the three brain regions. In recordings withou t cAMP in the internal solution, only 21% (12-15 days; n = 19) or none (16- 19 days; n = 7), respectively, showed a potassium current upon diazoxide ap plication. This metabolically regulated potassium conductance may be of imp ortance, particularly in immature astrocytes with a complex current pattern , which have a relatively high input resistance: K-ATP currents activated b y energy depletion may hyperpolarize the cells, or stabilize a negative res ting potential during depolarizing stimuli mediated, e.g., by glutamate rec eptors and/or uptake carriers. (C) 2000 Wiley-Liss, Inc.