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 mM 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 mM ATP. However, non-hydrolysable ATP analogs (a, beta-methylene ATP and beta,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.
Shoda
M
M
Heart Institute of Japan, Tokyo Women's Medical College, Japan.
Hagiwara
N
N
Kasanuki
H
H
Hosoda
S
S
D000241:Adenosine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology; D000249:Adenosine Monophosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D002412:Cations; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D004594:Electrophysiology / Q000379:methods*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*
D002412:Cations; D018118:Chloride Channels; D007473:Ion Channels; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000241:Adenosine