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

Abstract

1 Rat ventricular myocytes were dissociated and their responses to extracellularly applied ATP were recorded using patch pipettes under the whole cell configuration. 2 ATP initially induced an inward current followed by an outward current at -50 mV. With a Cs-rich pipette solution the late outward current was blocked, leaving a sustained inward current (IATP) suggesting that a K' conductance underlies the late response.3 When the extracellular Cl-concentration was changed, the reversal potential of IATPS corresponded well to the shift of the Cl-equilibrium potential. IATN was reversibly blocked by the chloride channel blocker, 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS).4 The concentration-response curve of IATh had a Hill coefficient of 0.98 and an ECM value of 5.2x 106M. 5 ATP was more potent than ADP, while AMP and adenosine were ineffective, suggesting that P2-purinoceptor activation induced IATPS* 6 The activation of IATPS was depressed by depleting the extracellular Mg2' and increased by adding 7 Our results strongly suggest that P2-purinoceptor activation by ATP induces both a Cl--conductance (IATPS) and a K+-conductance in rat ventricular myocytes.

β-Adrenergic stimulation does not activate Na+/Ca2+ exchange current in guinea pig, mouse, and rat ventricular myocytes

“…The lack of isoproterenol-activated Cl Ϫ current in mouse and rat ventricular cells is consistent with previous reports (18,24). In these myocytes, agonists to purinergic receptors activate the Cl Ϫ current (17,29,32). The cardiac Na ϩ /Ca 2ϩ exchange protein may indeed be phosphorylated by PKA (16,26,27), and its activity may be enhanced by PKA in heterogeneous expression systems (19,26).…”

Purinergic Inhibition of Glucose Transport in Cardiomyocytes

“…Extracellular ATP acting through purinergic receptors has been shown to exert pronounced effects on ionic currents and contractility in hearts and isolated cardiomyocytes (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)17). In this report, we present first evidence that in heart muscle cells ATP is also endowed with metabolic properties, in terms of a marked inhibition of glucose transport, independently of the electrical or mechanical activity of these cells.…”

“…As shown in Fig. 5C, extracellular ATP had no inhibitory action on the basal and dichloroacetate-stimulated rate of [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]pyruvate oxidation. On the contrary, ATP even tended to increase pyruvate oxidation in dichloroacetate-stimulated cells (Fig.…”

“…Finally, it was reported that in cardiomyocytes ATP activates trans-sarcolemmal bicarbonate/chloride exchange (10,11). We therefore also investigated the influence of the extracellular chloride concentration on the effect of the nucleotide on glucose transport.…”

“…More recent studies using isolated cardiomyocytes have shown that micromolar levels of extracellular ATP increase (i) plasma membrane conductances for cations (9) and also for chloride (10,11), (ii) the cytosolic calcium concentration (9,(12)(13)(14)(15), (iii) the rate of phosphoinositide hydrolysis (14,16,17), and (iv) the contraction amplitude (12,14,15). These results, along with pharmacological and immunohistochemical data (10, 11, 13, 14, 18 -20), suggest that members of both families of P 2 receptors are expressed in and linked to the electrical and contractile function of cardiac muscle cells.…”