Inhibition by extracellular ATP of L-type calcium channel currents in guinea-pig single sinoatrial nodal cells: Involvement of protein kinase C
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AbstractIt is generally accepted that ATP is costored and coreleased with noradrenaline from the sympathetic nerve terminals. The pacemaker region of the mammalian heart is highly innervated with the sympathetic nervous system. It is possible, therefore, that ATP released from nerve terminals can act on pacemaker cells and modulate heart beat activity. However, the physiological role(s) of extracellular ATP in mammalian heart beat has been little evaluated, even though the effect of extracellular ATP observed in in vivo studies has been attributed to the formation of adenosine, the catabolic product of ATP, which is a cardiodepressant. The present study investigated the effect of extracellular ATP on L-type calcium channel currents of guinea-pig single sinoatrial nodal cells, by using the whole cell patch clamp technique. Application of extracellular ATP caused a concentration-dependent and reversible inhibition of calcium channel currents with a 50% inhibitory concentration of 100 mu M The presence of the P-2-purinoceptor antagonist suramin (1, 10 and 100 mu M), reactive blue 2 (1 and 10 mu M) and pyridoxal phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 50 and 100 mu M) or the adenosine receptor anatgonists 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.1 mu M) and 8-phenyltheophylline (10 mu M) failed to affect the inhibitory action of extracellular ATP on cal cium channel currents. The relative rank order of potency of different nucleotides and nucleosides, at a concentration of 100 mu M, on the inhibition of calcium channel currents was as follows: ATP = alpha,beta-methylene-ATP much greater than 2-methylthioATP greater than or equal to adenosine 5'-O-(3-thiotriphosphate) much greater than UTP = ADP > AMP greater than or equal to adenosine. Dialysis, by way of the patch pipette, of the cell interior with specific protein kinase C inhibitor staurosporine (70 nM) or calphostin C (500 nM) abolished extracellular ATP-induced inhibition of calcium channel currents. Therefore, extracellular ATP-mediated inhibition of calcium channel currents in guineapig single sinoatrial nodal cells involves activation of protein kinase C.
All Author(s) ListKwan YW, Qi AD
Journal nameCanadian Journal of Cardiology
Volume Number13
Issue Number12
Pages1202 - 1211
LanguagesEnglish-United Kingdom
Keywordsextracellular ATP; heart beat; L-type calcium channel current; sinoatrial nodal cells
Web of Science Subject CategoriesCardiac & Cardiovascular Systems; CARDIAC & CARDIOVASCULAR SYSTEMS; Cardiovascular System & Cardiology

Last updated on 2020-14-10 at 00:44