ATP-ACTIVATED CATIONIC CURRENT IN RABBIT SINOATRIAL NODE CELLS

The electrophysiological effect of extracellular ATP was investigated in voltage-clamped single cells from the rabbit sino-atrial node. Exte rnal 0.5 mM ATP consistently activated a time-independent, weakly inwa rdly rectifying current (2.26 +/- 0.14 pA/pF at - 100 mV, n = 23). Thi s external ATP-activated current increased in a dose-dependent manner over the concentration range 0.01 to 1 mM. ATP. However, non-hydrolysa ble ATP analogs (alpha,beta-methylene ATP and beta,r-methylene ATP) fa iled to activate this current. Moreover, adenosine, adenosine monophos phate and adenosine diphosphate were all ineffective in eliciting the ATP-activated current over the concentration range 0.5 to 1 mM, sugges ting that it is regulated via the P-2-purinoreceptor, The permeability sequence for the ATP-activated current among different cations (deter mined from reversal potential measurements) was 1.99: 1: 1: 0.24: 0.22 for K+, Na+, Cs+, Tris and N-methyl-D-glucamine. The current componen t was not affected by substitution of external Cl- by aspartate or by the application of a stilbene-derivative Cl- channel blocker. Thus, th e ATP-activated current in rabbit sinoatrial node cells was non-select ive for monovalent cations, and could be carried by large molecular io ns, such as N-methyl-D-glucamine or Tris. We suggest that it might mak e some contribution to the chronotropic effects seen on release of tra nsmitters from autonomic nerve endings in the heart. (C) 1997 Academic Press Limited.