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

Abstract

The pharmacological profile of the ATP‐induced increase in ICa amplitude and of ATP activation of a non‐specific cationic current, IATP, was investigated in rat ventricular cells. The EC50 values for ICa increase and IATP activation were 0.36 μm and 0.76 μm respectively. Suramin (10 μm) and cibacron blue (1 μm) competitively antagonized both effects of ATP. The rank order of efficacy and potency of ATP analogues in increasing ICa amplitude was 2‐methylthio‐ATP ≅ ATP ≅ ATPγS. The derivatives α,β‐methylene‐ATP, β,γ‐methylene‐ATP and β,γ‐imido‐ATP up to 500 μm had no significant effects. The rank order of efficacy of ATP analogues in activating a non‐specific cationic current, IATP, was 2‐methylthio‐ATP > ATP > > ATPγS. The rank order of potency was 2‐methylthio‐ATP ≅ ATP. The EC50 of ATPγS could not be determined owing to its very low efficacy. The ATP analogues α,β‐methylene‐ATP, β,γ‐methylene‐ATP and β,γ‐imido‐ATP at 500 μm did not activate IATP but acted as antagonists of activation of IATP by ATP. The results suggest that the increase in ICa amplitude induced by external ATP is due to activation of P2Y‐purinoceptors. The mechanism of IATP activation remains to be determined before the receptor subtype involved can be deduced. 1994 British Pharmacological Society