Effects of extracellular ATP on ICa, [Ca2+]i, and contraction in isolated ferret ventricular myocytes.
The effects of extracellular ATP on the voltage-activated "L-type" Ca current (ICa), action potential, resting and transient intracellular Ca2+ levels, and cell contraction were examined in enzymatically isolated myocytes from the right ventricles of ferrets. With the use of the whole cell patch-clamp technique, extracellular ATP (10(-7) to 10(-3) M) inhibited ICa in a time- and concentration-dependent manner. ATP decreased the peak amplitude of ICa without altering the residual current at the end of 500-ms clamp steps. The concentration-response relationship for ATP inhibition of ICa was well described by a conventional Michaelis-Menten relationship with a half-maximal inhibitory concentration of 1 microM and a maximal effect of 50%. Consistent with its inhibitory effect on ICa, ATP hyperpolarized the plateau phase and shortened the action potential duration. In fura-2-loaded myocytes, extracellular ATP did not change the resting myoplasmic Ca2+ levels; however, when current was elicited under voltage-clamp conditions, ATP both decreased the myoplasmic intracellular Ca2+ transient and inhibited the degree of cell shortening. Our results suggest that ATP could be a genuine and potent extracellular modulator of cardiac function in ferret ventricular myocardium.
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Y
Y
Qu
H M
HM
Himmel
D L
DL
Campbell
H C
HC
Strauss
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005289:Ferrets / Q000502:physiology*; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects / Q000502:physiology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D017202:Myocardial Ischemia / Q000503:physiopathology; D009206:Myocardium / Q000166:cytology*; D013997:Time Factors; D016276:Ventricular Function
D015220:Calcium Channels; D000255:Adenosine Triphosphate; D002118:Calcium