Stimulation of cardiac L-type calcium channels by extracellular ATP.
The co-release of ATP with norepinephrine from sympathetic nerve terminals in the heart may augment adrenergic stimulation of cardiac Ca(2+) channel activity. To test for a possible direct effect of extracellular ATP on L-type Ca(2+) channels, single channels were reconstituted from porcine sarcolemma into planar lipid bilayers so that intracellular signaling pathways could be controlled. Extracellular ATP (2-100 microM) increased the open probability of the reconstituted channels, with a maximal increase of approximately 2.6-fold and an EC(50) of 3.9 microM. The increase in open probability was due to an increase in channel availability and a decrease in channel inactivation rate. Other nucleotides displayed a rank order of effectiveness of ATP > alpha,beta-methylene-ATP > 2-methylthio-ATP > UTP > adenosine 5'-O-(3-thiotriphosphate) >> ADP; adenosine had no effect. Several antagonists of P2 receptors had no impact on the ATP-dependent increase in open probability, indicating that receptor activation was not required. These results suggest that extracellular ATP and other nucleotides can stimulate the activity of cardiac L-type Ca(2+) channels via a direct interaction with the channels.
Liu
Q Y
QY
Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7365, USA.
Rosenberg
R L
RL
D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D005110:Extracellular Space / Q000502:physiology; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008051:Lipid Bilayers / Q000737:chemistry; D018408:Patch-Clamp Techniques; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D012508:Sarcolemma / Q000502:physiology*; D013552:Swine; D014529:Uridine / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
D020746:Calcium Channels, L-Type; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; C057561:1-palmitoyl-2-oleoylphosphatidylethanolamine; D000255:Adenosine Triphosphate; D000241:Adenosine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; D014544:Uridine Triphosphate; D014529:Uridine