Excitatory effect of ATP on rat area postrema neurons.

ABSTRACT: ATP-induced inward currents and increases in the cytosolic Ca(2+) concentration ([Ca](in)) were investigated in neurons acutely dissociated from rat area postrema using whole-cell patch-clamp recordings and fura-2 microfluorometry, respectively. The ATP-induced current (I (ATP)) and [Ca](in) increases were mimicked by 2-methylthio-ATP and ATP-gammaS, and were inhibited by P2X receptor (P2XR) antagonists. The current-voltage relationship of the I (ATP) exhibited a strong inward rectification, and the amplitude of the I (ATP) was concentration-dependent. The I (ATP) was markedly reduced in the absence of external Na(+), and the addition of Ca(2+) to Na(+)-free saline increased the I (ATP). ATP did not increase [Ca](in) in the absence of external Ca(2+), and Ca(2+) channel antagonists partially inhibited the ATP-induced [Ca](in) increase, indicating that ATP increases [Ca](in) by Ca(2+) influx through both P2XR channels and voltage-dependent Ca(2+) channels. There was a negative interaction between P2XR- and nicotinic ACh receptor (nAChR)-channels, which depended on the amplitude and direction of current flow through either channel. Current occlusion was observed at V (h)s between -70 and -10 mV when the I (ATP) and ACh-induced current (I (ACh)) were inward, but no occlusion was observed when these currents were outward at a V (h) of +40 mV. The I (ATP) was not inhibited by co-application of ACh when the I (ACh) was markedly decreased either by removal of permeant cations, by setting V (h) close to the equilibrium potential of I (ACh), or by the addition of d-tubocurarine or serotonin. These results suggest that the inhibitory interaction is attributable to inward current flow of cations through the activated P2XR- and nAChR-channels.

SUBMITTER: Sorimachia M 

PROVIDER: S-EPMC2096647 | biostudies-other | 2006 Sep

REPOSITORIES: biostudies-other