Referenced in: none

Automatically associated channels: Kir2.3

Title: Extracellular ATP-induced currents in astrocytes: involvement of a cation channel.

Authors: W Walz, G Gimpl, C Ohlemeyer, H Kettenmann

Journal, date & volume: J. Neurosci. Res., 1994 May 1 , 38, 12-8

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/7520086

Abstract
Whole-cell currents were measured with the perforated patch clamp technique in cultured rat astrocytes to analyze the underlying ionic mechanism for a P2-purinoceptor-mediated depolarization. ATP (100 microM) induced an inward current with a mean amplitude of 130 pA and an EC50 of 17 microM. The response desensitized during a 1 min application. Replacement of extracellular Na+ with NMDG or K+ abolished the ATP-evoked inward current. Replacement of Na+ with choline, however, resulted in an ATP-evoked response of one-third the amplitude in normal solution. This is indicative of a cation rather than Na+ channel. However, due to difficulties in voltage-clamping these gap junction-coupled cells at voltages different from the membrane resting potential, the current reversal potential could not be determined. Measurements with K(+)-sensitive microelectrodes showed that 100 microM ATP lowered the intracellular K+ concentration. Replacement of extracellular Ca2+ or Cl- did not alter the ATP-induced inward currents. Fura-2 imaging experiments revealed a transient rise of the intracellular Ca2+ concentration during ATP application. Removal of extracellular Ca2+ did not influence the peak response; it did, however, shorten the time course. These results and previous observations that the permeability changes are caused by a P2x receptor are indicative of an ATP-sensitive cation conductance. In addition, cytoplasmic Ca2+ is increased by mobilization from intracellular stores, and by additional influx across the cell membrane. Extracellular ATP released by neurons could evoke K+ release from astrocytes as well as be a mediator for cation changes that signal cell activation processes when released by damaged cells.