Sequential and opposite regulation of two outward K(+) currents by ET-1 in cultured striatal astrocytes.
In the brain, astrocytes represent a major target for endothelins (ETs), a family of peptides that can be released by several cell types and that have potent and multiple effects on astrocytic functions. Four types of K(+) currents (I(K)) were detected in various proportions by patch-clamp recordings of cultured striatal astrocytes, including the A-type I(K), the inwardly rectifying I(K IR), the Ca(2+)-dependent I(K) (I(K Ca)), and the delayed-rectified I(K) (I(K DR)). Variations in the shape of current-voltage relationships were related mainly to differences in the proportion of these currents. ET-1 was found to regulate with opposite effects the two more frequently recorded outward K(+) currents in striatal astrocytes. Indeed, this peptide induced an initial activation of I(K Ca) (composed of SK and BK channels) and a delayed long-lasting inhibition of I(K DR). In current-clamp recordings, the activation of I(K Ca) correlated with a transient hyperpolarization, whereas the inhibition of I(K DR) correlated with a sustained depolarization. These ET-1-induced sequential changes in membrane potential in astrocytes may be important for the regulation of voltage gradients in astrocytic networks and the maintenance of K(+) homeostasis in the brain microenvironment.
Bychkov
R
R
Institut National de la Santé et de la Recherche Médicale Unité U114, Collège de France, 75231 Paris, Cedex 05, France.
Glowinski
J
J
Giaume
C
C
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology*; D019332:Endothelin-1 / Q000494:pharmacology*; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D019789:Tetraethylammonium / Q000494:pharmacology
D019332:Endothelin-1; D010455:Peptides; D015221:Potassium Channels; D019789:Tetraethylammonium; C064719:iberiotoxin; D015761:4-Aminopyridine; D002118:Calcium