Enhancement of intracellular Cl- concentrations induced by extracellular ATP in guinea pig ventricular muscle

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 (pH(i)) 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 pH(i), 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.