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Modulation by extracellular ATP of L‐type calcium channels in guinea‐pig single sinoatrial nodal cell
Author(s) -
Qi AiDong,
Kwan Yiu Wa
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16058.x
Subject(s) - adenosine , suramin , ppads , biophysics , medicine , chemistry , patch clamp , adenosine triphosphate , endocrinology , biology , purinergic receptor , biochemistry , receptor
1 The effects of extracellular adenosine 5′‐triphosphate ([ATP] 0 ) on the L‐type Ca 2+ channel currents in guinea‐pig single sinoatrial nodal (SAN) cells, isolated by enzymatic dissociation, were investigated by use of whole‐cell patch‐clamp techniques. 2 The application of [ATP] 0 (2 μ m ‐1 mM) produced an inhibitory effect on the L‐type Ca 2+ channel current peak amplitude (10 mM Ba 2+ as charge carrier) in a concentration‐dependent and reversible manner with an IC 50 of 100 μ m and a Hill coefficient of 1.83. 3 The presence of the adenosine receptor antagonists, 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX, 0.1 μ m ) and 8‐phenyltheophylline (10 μ m ) did not affect the [ATP] O ‐induced inhibition of the Ca 2+ channel currents. Adenosine (100 μ m ) had little effect on the basal Ca 2+ channel currents. Adenosine 500 μ m , caused 23% inhibition of the Ca 2+ channel current, which was abolished by 0.1 μ m DPCPX. 4 The presence of the P 2 ‐purinoceptor antagonists, suramin (1, 10 and 100 μ m ), reactive blue 2 (1 and 10 μ m ) and pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS, 50 and 100 μ m ) failed to affect the inhibitory action of [ATP] 0 on Ca 2+ channel currents. 5 The relative rank order of potency of different nucleotides and nucleosides, at a concentration of 100 μ m , on the inhibition of the Ca 2+ channel currents is as follows: adenosine 5′‐triphosphate (ATP) = α, β‐methylene‐ATP (α, βMeATP) > > 2‐methylthioATP (2‐MeSATP) ≥ adenosine 5′‐O‐(3‐thiotriphosphate) (ATPγS) > > uridine 5′‐triphosphate (UTP) = adenosine 5′‐diphosphate (ADP) > adenosine 5′‐monophosphate (AMP) ≥ adenosine. 6 These results suggest that [ATP] 0 may play an important role in the heart beat by inhibiting the L‐type Ca 2+ channel currents in single SAN cells. This inhibitory effect is not due to the formation of adenosine resulting from the enzymatic degradation of [ATP] 0 . Based on the relative order of inhibitory potency of different nucleotides and nucleosides on the L‐type Ca 2+ channel currents and the ineffectiveness of the purinoceptor antagonists tested, a novel type of purinoceptor may be involved.