ATP-activated Cationic Current in Rabbit Sino-atrial Node Cells

The electrophysiological effect of extracellular ATP was investigated in voltage-clamped single cells from the rabbit sino-atrial node. External 0.5 m ATP consistently activated a time-independent, weakly inwardly rectifying current (2.26±0.14 pA/pF at −100 mV,n=23). This external ATP-activated current increased in a dose-dependent manner over the concentration range 0.01 to 1 m ATP. However, non-hydrolysable ATP analogs (a,β-methylene ATP andβ,r-methylene ATP) failed to activate this current. Moreover, adenosine, adenosine monophosphate and adenosine diphosphate were all ineffective in eliciting the ATP-activated current over the concentration range 0.5 to 1 m , suggesting that it is regulated via the P2-purinoreceptor. The permeability sequence for the ATP-activated current among different cations (determined from reversal potential measurements) was 1.09: 1: 1: 0.24: 0.22 for K+, Na+, Cs+, Tris and N-methyl-D-glucamine. The current component was not affected by substitution of external Cl−by aspartate or by the application of a stilbene-derivative Cl−channel blocker. Thus, the ATP-activated current in rabbit sino-atrial node cells was non-selective for monovalent cations, and could be carried by large molecular ions, such as N-methyl-D-glucamine or Tris. We suggest that it might make some contribution to the chronotropic effects seen on release of transmitters from autonomic nerve endings in the heart.