ATP increases [Ca2+ ]i and activates a Ca2+ -dependent Cl- current in rat ventricular fibroblasts

Experimental Physiology
Noriyuki HatanoW R Giles

Abstract

What is the central question of this study? Although electrophysiological and biophysical characteristics of heart fibroblasts have been studied in detail, their responses to prominent paracrine agents in the myocardium have not been addressed adequately. Our experiments characterize changes in cellular electrophysiology and intracellular calcium in response to ATP. What is the main finding and its importance? In rat ventricular fibroblasts maintained in cell culture, we find that ATP activates a specific subset of Ca2+ -activated Cl- channels as a consequence of binding to P2Y purinoceptors and then activating phospholipase C. This response is not dependent on [Ca2+ ]o but requires an increase in [Ca2+ ]i and is modulated by the type of nucleotide that is the purinergic agonist. Effects of ATP on enzymatically isolated rat ventricular fibroblasts maintained in short-term (36-72 h) cell culture were examined. Immunocytochemical staining of these cells revealed that a fibroblast, as opposed to a myofibroblast, phenotype was predominant. ATP, ADP or uridine 5'-triphosphate (UTP) all produced large increases in [Ca2+ ]i . Voltage-clamp studies (amphotericin-perforated patch) showed that ATP (1-100 μm) activated an outwardly rectif...Continue Reading

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