Identification of P_2Y purinoceptors associated with voltage‐activated cation channels in cardiac ventricular myocytes of the rat

Abstract

Extracellular ATP has vasodilatory and inotropic effects in the heart. We have demonstrated that extracellular ATP, in a concentration-dependent manner (1 0 nM -0.1 mM), increased [Ca' 'Ii in suspensions of isolated fura-2-loaded rat cardiac ventricular myocytes (maximum 96 f 10% increase over basal levels, SEM, n = 12, P < 0.01).The increase in [Ca2+Ii was often biphasic, with an initial fast phase ( < 1 s) of low amplitude, followed by a slower phase of higher amplitude. A second application of ATP had little effect, and ATP abolished the effect of subsequent electrical stimulations, even through the cells were still able to respond with an increase in [CaZ+Ii to KCI-

Extracellular ATP-induced acidification leads to cytosolic calcium transient rise in single rat cardiac myocytes

“…The Ca2+ rise as previously reported by others [7,24,26,27] and during the present work has at least three origins. (1) [7][8][9] to the deleterious ventricular arrhythmias expected from the above results.…”

“…Moreover, Sharma & Sheu [24] and De Young & Scarpa [25,26] showed that ATP triggered a large Ca2+ transient, followed by a weaker sustained increase, whereas others [7] found only a slow rise in intracellular Ca2". More recently, ATP was demonstrated to trigger a membrane depolarization associated with the rapid Ca2+ transient [27]. These effects of ATP on…”

Activation of chloride current by P2‐purinoceptors in rat ventricular myocytes

“…The subtype classification of P2-purinoceptor therefore remains to be determined although our data might also indicate the presence of P2y-purinoceptors in rat ventricular myocytes (Bjornsson et al, 1989).…”

Pharmacological profile of the ATP‐mediated increase in L‐type calcium current amplitude and activation of a non‐specific cationic current in rat ventricular cells

“…This decrease in ICa has been attributed to occupancy of P2y-purinoceptors, with 2-methylthio-ATP being more potent than a,-methylene-ATP (Qu et al, 1993b). The transient increase in Ca, (in rat) and the positive inotropism ( in rat and guinea pig) induced by ATP have also been attributed to P2y purinoceptors (Bjornsson et al, 1989;Mantelli et al, 1993;Wang et al, 1993). In the present study we have investigated the pharmacological profile of ATP-activated non-specific cationic current and the increase in Ica in rat ventricular myocytes, which are supposed to be largely responsible for the changes in Ca, and the positive inotropism.…”

“…In rat cardiac preparations, ATP is reported to have positive inotropic effects and to increase the Ca2+ transients of electrically stimulated cells (Danziger et al, 1988;Legssyer et al, 1988). It has also been reported that ATP transiently increases the intracellular Ca2' concentration, Ca,, of quiescent cells (De Young & Scarpa, 1987;Danziger et al, 1988;Bjornsson et al, 1989;Puceat et al, 1991a;Hirano et al, 1991). In addition, electrophysiological studies have shown that ATP activates a nonspecific cationic current in frog, rat and guinea pig cardiac cells (Friel & Bean, 1988;; Matsuura & Ehara, 1992), an inwardly rectifying K+ channel in frog (Friel & Bean, 1990) and a chloride current in guinea pig (Matsuura & Ehara, 1992), increases the L-type calcium current amplitude in rat Zheng et al, 1993) and increases both the L-and T-type in frog cells (Alvarez & Vassort, 1992).…”