Modulation by extracellular ATP of two distinct currents in rat myocytes.
The whole cell voltage-clamp technique was used to study the electrophysiological effects induced by ATP in isolated ventricular myocytes. ATP or 2-methylthio-ATP evoked a transient inward current (IATP) when the transmembrane potential (Vm) was held at -70 mV and increased the Ca2+ current (ICa) when Vm was depolarized to 0 mV. The time course of IATP was fitted by a single exponential equation with a brief time constant (165 ms), whereas the time course of enhancement of ICa by ATP was also fitted by a single exponential equation with a much longer time constant (14 s). IATP was much less pronounced when extracellular Mg2+ was absent, and it was insensitive to dihydropyridines. In contrast, the enhancement of ICa by ATP was not affected by removing extracellular Mg2+, but it was suppressed by Ca2+ channel blockers. Both IATP and ICa were decreased by extracellular Cd2+. Internally applied guanosine 5'-O-(2-thiodiphosphate), which prevents the activation of G proteins, abolished the ATP-enhanced rise in ICa but did not inhibit IATP. These data suggest that ATP elicits IATP and increases ICa through two different mechanisms. IATP appears to be generated via receptor-operated channels that are activated by ATP. The ATP-induced increase of ICa appears to be mediated by G proteins via pathways that are independent of adenosine 3',5'-cyclic monophosphate and phosphoinositide turnover.
Zheng
J S
JS
Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106.
Christie
A
A
Levy
M N
MN
Scarpa
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004553:Electric Conductivity; D005110:Extracellular Space / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D008274:Magnesium / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D015290:Second Messenger Systems; D013873:Thionucleotides / Q000494:pharmacology
D002121:Calcium Channel Blockers; D013873:Thionucleotides; D006153:Guanosine Diphosphate; C023427:guanosine 5'-O-(2-thiodiphosphate); D000255:Adenosine Triphosphate; D008274:Magnesium; D002118:Calcium