Zhong-Fang Lai* and Katsuhide Nishi
Department of Pharmacology, Kumamoto University School of Medicine, 2-2-1
Honjo, Kumamoto 860-0811, Japan
*Corresponding author.ﾊﾊFAX:+81-96-373-5082
E-mail: lai-zf@gpo.kumamoto-u.ac.jp
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ﾊ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ﾊ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
Copyrightｩ The Japanese Pharmacological Society 2000
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