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

• Published in: Journal of molecular and cellular cardiology 1997-02, Vol.29 (2), p.689-695
• Main Authors: Shoda, Morio, Hagiwara, Nobuhisa, Kasanuki, Hiroshi, Hosoda, Saichi
• Format: Article
• Language: English
• Subjects: Adenosine - pharmacology; Adenosine Diphosphate - pharmacology; Adenosine Monophosphate - pharmacology; Adenosine triphosphate; Adenosine Triphosphate - analogs & derivatives; Adenosine Triphosphate - pharmacology; Animals; Cations; Chloride Channels - drug effects; Chloride Channels - physiology; Electrophysiology - methods; Ion Channels - drug effects; Ion Channels - physiology; Non-selective cation current; P2-purinergic receptor; Rabbits; Sino-atrial node cell; Sinoatrial Node - cytology; Sinoatrial Node - drug effects; Sinoatrial Node - physiology; Whole-cell voltage clamp
• ISSN: 0022-2828; 1095-8584
• DOI: 10.1006/jmcc.1996.0311

The electrophysiological effect of extracellular ATP was investigated in voltage-clamped single cells from the rabbit sino-atrial node. External 0.5 mmATP 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 mmATP. 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 mm, 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.