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Developmental downregulation of ATP‐sensitive potassium conductance in astrocytes in situ
Author(s) -
Brockhaus Johannes,
Deitmer Joachim W.
Publication year - 2000
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/1098-1136(200012)32:3<205::aid-glia10>3.0.co;2-6
Subject(s) - diazoxide , potassium channel , biophysics , biology , patch clamp , potassium , membrane potential , medicine , potassium channel blocker , endocrinology , cerebellum , adenosine triphosphate , biochemistry , neuroscience , chemistry , electrophysiology , insulin , organic chemistry
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. GLIA 32:205–213, 2000. © 2000 Wiley‐Liss, Inc.