Jpn. J. Pharmacol. 84 (4), 438-448 (2000)

Enhancement of Intracellular Cl- Concentrations Induced by Extracellular ATP in Guinea Pig Ventricular Muscle

Zhong-Fang Lai* and Katsuhide Nishi

Department of Pharmacology, Kumamoto University School of Medicine, 2-2-1 Honjo, Kumamoto 860-0811, Japan
*Corresponding author.╩╩FAX:+81-96-373-5082

Abstract: We investigated effects of extracellular ATP on intracellular chloride activities ([Cl-]i) and possible contribution of the Cl--HCO3- exchange to this increase in [Cl-]i in isolated guinea pig ventricular muscles. The [Cl-]i and intracellular pH (pHi) were recorded in quiescent ventricular muscles using double-barreled ion-selective microelectrode techniques. MgATP at a concentration higher than 0.1╩mM, induced an increase in [Cl-]i, and this increase in [Cl-]i was dependent on the concentration of ATP but not on the concentration of magnesium ions present in the perfusion solution. NaADP, but not NaAMP, at a concentration of 0.5╩mM induced a similar increase in [Cl-]i as that induced by MgATP. However, the NaADP-induced increase in [Cl-]i was transient and gradually returned to the control level even though NaADP was continuously present. Furthermore, ATP also triggered a transient acidification of pHi, and both increases in [Cl-]i and intracellular H+ induced by ATP were prevented when preparations were pretreated with stilbene derivatives, SITS and DIDS, or perfused with a Cl--free solution. Our findings showed that the increased extracellular ATP concentrations might trigger an increase in [Cl-]i in ventricular muscles. In light of previous studies showing that cardiac ischemia induced increases in extracellular nucleotide concentrations and [Cl-]i in ventricular muscles, we propose that ischemia-induced accumulation of ATP concentration in the extracellular space may be an important factor to trigger increment of [Cl-]i during ischemic conditions.

Keywords: Extracellular ATP, Intracellular chloride activity, Ion-selective microelectrode,
Cl--HCO3- exchange

Copyrightę The Japanese Pharmacological Society 2000

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