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 (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.
Lai
Z F
ZF
Department of Pharmacology, Kumamoto University School of Medicine, Japan. lai-zf@gpo.kumamoto-u.ac.jp
Nishi
K
K
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D017920:Antiporters / Q000187:drug effects* / Q000378:metabolism; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism
D017920:Antiporters; D027963:Chloride-Bicarbonate Antiporters; D002712:Chlorides; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid