Effects of anions on ATP-activated nonselective cation current in NG108-15 cells. Hiromi Kaiho, Junko Kimura, Isao Matsuoka and Hironori Nakanishi. Department of Pharmacology, Fukushima Medical Collage, Hikarigaoka 1, Fukushima 960-12, Japan, (Tel) 81- (245) 48-2111 (Ext. 2153), (Fax) 81- (245) 48-0575.
APStracts 4:0019N, 1997.
ABSTRACT
Extracellular ATP induces a nonselective cation current and elevates intracellular Ca2+ concentration ([Ca2+]i) via P2Z receptor in NG108-15 cells. We found that the ATP-induced nonselective cation current became larger in methanesulfonic acid (MS-) than in Cl- external solution. We therefore examined the effects of various external anions on the ATP-induced cation current using the whole-cell patch clamp technique. The concentration-response curves for ATP were obtained in different anionic external solutions. The maximum current density (Imax) and the EC50 value of ATP were obtained by fitting the curves using the Hill coefficient of 2. The apparent Imax decreased in the order of aspartic acid (Asp-) > MS- > F- > Cl- > Br- ³ I-. The apparent EC50 values for ATP were shifted to the right in the sequence of Asp- < F- < MS- < Br- < Cl- < I-. Thus both Imax and EC50 values were affected by anions, indicating that anions are mixed type inhibitors of the ATP-induced current. The shift of the EC50 values of ATP indicates that anions interfere with ATP binding to the receptor. External Cl- was a noncompetitive inhibitor with respect to external Na+, a major cation carrying the ATP-induced current. We conclude that extracellular anions inhibit the ATP-induced nonselective cation current at least partly by interfering with ATP-binding to the P2Z receptor, which is associated with the nonselective cation channels. 

Received 15 October 1996; accepted in final form 2 January 1996.
APS Manuscript Number J825-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 24 January 1997