Depression of excitability by sphingosine 1-phosphate in rat ventricular myocytes.
Sphingosine 1-phosphate (S-1-P) is a bioactive sphingolipid that is released from activated platelets. Extracellular S-1-P augments an inwardly rectifying potassium conductance in cultured atrial preparations, but the electrophysiological effects of this compound in the ventricle are unknown. The electrophysiological effects of S-1-P were examined in single myocytes from rat ventricular muscle. Action potential waveforms and underlying ionic currents in the presence and absence of 3 microM S-1-P (1-6 min) were recorded. S-1-P increased the minimum stimulus current needed to elicit an action potential by approximately 100 pA. Pertussis toxin or preexposure to S-1-P did not alter this effect. The action potential waveform was unchanged by S-1-P. The inward sodium current (INa) was examined in a range of membrane potentials just negative to the potential for firing an action potential. S-1-P reversibly inhibited peak INa by approximately 50 pA, whereas the inward rectifier potassium current was not significantly changed. The results of this study suggest that S-1-P inhibits rat ventricular excitability by reducing INa.
MacDonell
K L
KL
Department of Pharmacology and Therapeutics, Heritage Medical Research Centre, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Severson
D L
DL
Giles
W R
WR
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002469:Cell Separation; D004056:Differential Threshold / Q000187:drug effects; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000187:drug effects / Q000502:physiology; D008246:Lysophospholipids; D008297:Male; D009206:Myocardium / Q000166:cytology; D037342:Pertussis Toxin; D011188:Potassium / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000502:physiology; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000502:physiology; D013997:Time Factors; D016276:Ventricular Function / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D008246:Lysophospholipids; D010566:Virulence Factors, Bordetella; C060506:sphingosine 1-phosphate; D012964:Sodium; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D013110:Sphingosine; D011188:Potassium