MODULATION BY EXTRACELLULAR ATP OF L-TYPE CALCIUM CHANNELS IN GUINEA-PIG SINGLE SINOATRIAL NODAL CELL

1 The effects of extracellular adenosine 5'-triphosphate ([ATP](o)) on the L-type Ca2+ channel currents in guinea-pig sinoatrial nodal (SAN) cells, isolated by enzymatic dissociation, were investigated by use o f whole-cell patch-clamp techniques. 2 The application of [ATP](o) (2 mu M-1 mM) produced an inhibitory effect on the L-type Ca2+ channel cu rrent peak amplitude (10 mM Ba2+ as charge carrier) in a concentration -dependent and reversible manner with an IC50 of 100 mu M and a Hill c oefficient of 1.83. 3 The presence of the adenosine receptor antagonis ts, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.1 mu M) and 8-phenylt heophyline (10 mu M) did not affect the [ATP](o)-induced inhibition of the Ca2+ channel currents. Adenosine (100 mu M) had little effect on the basal Ca2+ channel currents. Adenosine 500 mu M, caused 23% inhibi tion of the Ca2+ channel current, which was abolished by 0.1 mu M DPCP X. 4 The presence of the P-2-purinoceptor antagonists, 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) failed to affect the inhibitory action of [ATP](o) on Ca2+ channel currents. 5 T he relative rank order of potency of different nucleosides, at a conce ntration of 100 mu M, on the inhibition of the Ca2+ channel currents i s as follows: adenosine 5'-triphosphate (ATP) = alpha,beta-methylene-A TP (alpha,beta MeATP) much greater than 2-methylthioATP (2-MeSATP) gre ater than or equal to adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S ) much greater than uridine 5'-triphosphate (UTP) = adenosine 5'-dipho sphate (ADP) > adenosine 5'-monophosphate (AMP) greater than or equal to adenosine. 6 These results suggests that [ATP](o) may play an impor tant role in the heart beat by inhibiting the L-type Ca2+ channel curr ents in single SAN cells. This inhibitory effect is not due to the for mation of adenosine resulting from the enzymatic degradation of [ATP]( o). Based on the relative order of inhibitory potency of different nuc leotides and nucleosides on the L-type Ca2+ channel currents and the i neffectiveness of the purinoceptor antagonists tested, a novel type of purinoceptor may be involved.