Developmental downregulation of ATP-sensitive potassium conductance in astrocytes in situ.
In many neural and non-neural cells, ATP-sensitive potassium (K(ATP)) channels couple the membrane potential to energy metabolism. We investigated the activation of K(ATP) currents in astrocytes of different brain regions (hippocampus, cerebellum, dorsal vagal nucleus) by recording whole-cell currents with the patch-clamp technique in acute rat brain slices. Pharmacological tools, hypoglycemia and specific compounds in the pipette solution (cAMP, UDP), were used to modulate putative K(ATP) currents. The highest rate of K(ATP) specific currents was observed with a pipette solution containing cAMP and external stimulation with diazoxide (0.3 mM). The diazoxide-activated current had a reversal potential negative to -80 mV and was inhibited by tolbutamide (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 developmentally downregulated. Whereas diazoxide activated K(ATP) currents in 57% 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 significant difference was observed for the three brain regions. In recordings without 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 application. This metabolically regulated potassium conductance may be of importance, particularly in immature astrocytes with a complex current pattern, which have a relatively high input resistance: K(ATP) currents activated by energy depletion may hyperpolarize the cells, or stabilize a negative resting potential during depolarizing stimuli mediated, e.g., by glutamate receptors and/or uptake carriers.
Brockhaus
J
J
Abteilung Allgemeine Zoologie, Fachbereich Biologie, Universität Kaiserslautern, Kaiserslautern, Germany. jbrock@rhrk.uni-kl.de
Deitmer
J W
JW
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000502:physiology*; D016922:Cellular Senescence / Q000502:physiology*; D002531:Cerebellum / Q000166:cytology; D000242:Cyclic AMP / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology; D004553:Electric Conductivity; D005947:Glucose / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000378:metabolism*; D051381:Rats; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D014044:Tolbutamide / Q000494:pharmacology; D014630:Vagus Nerve / Q000166:cytology; D014665:Vasodilator Agents / Q000494:pharmacology
D007004:Hypoglycemic Agents; D015221:Potassium Channels; D013453:Sulfonylurea Compounds; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D014044:Tolbutamide; D000242:Cyclic AMP; D005947:Glucose; D003981:Diazoxide