Cardiac myocyte excitation by ultrashort high-field pulses.
In unexcitable, noncardiac cells, ultrashort (nanosecond) high-voltage (megavolt-per-meter) pulsed electrical fields (nsPEF) can mobilize intracellular Ca2+ and create transient nanopores in the plasmalemma. We studied Ca2+ responses to nsPEF in cardiac cells. Fluorescent Ca2+ or voltage signals were recorded from isolated adult rat ventricular myocytes deposited in an electrode microchamber and stimulated with conventional pulses (CPs; 0.5-2.4 kV/cm, 1 ms) or nsPEF (10-80 kV/cm, 4 ns). nsPEF induced Ca2+ transients in 68/104 cells. Repeating nsPEF increased the likelihood of Ca2+ transient induction (61.8% for <10 nsPEF vs. 80.6% for > or =10 nsPEF). Repetitive Ca2+ waves arising at the anodal side and Ca2+ destabilization occurred after repeated nsPEF (12/29) or during steady-state single nsPEF delivery at 2 Hz. Removing extracellular Ca2+ abolished responses to nsPEF. Verapamil did not affect nsPEF-induced Ca2+ transients, but decreased responses to CP. Tetrodotoxin and KB-R7943 increased the repetition threshold in response to nsPEF: 1-20 nsPEF caused local anodal Ca2+ waves without Ca2+ transients, and > or =20 nsPEF caused normal transients. Ryanodine-thapsigargin and caffeine protected against nsPEF-induced Ca2+ waves and showed less recovery of diastolic Ca2+ levels than CP. Voltage recordings demonstrated action potentials triggered by nsPEF, even in the presence of tetrodotoxin. nsPEF can mobilize intracellular Ca2+ in cardiac myocytes by inducing action potentials. Anodal Ca2+ waves and resistance to Na+ and Ca2+ channel blockade suggest nonselective ion channel transport via sarcolemmal nanopores as a triggering mechanism.
Wang
Sufen
S
Division of Cardiac Electrophysiology, Department of Cardiology, The Methodist Hospital, Houston, Texas, USA.
Chen
Jiexiao
J
Chen
Meng-Tse
MT
Vernier
P Thomas
PT
Gundersen
Martin A
MA
Valderrábano
Miguel
M
D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods; D005110:Extracellular Space / Q000737:chemistry; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D002121:Calcium Channel Blockers; D026941:Sodium Channel Blockers; D012433:Ryanodine; D002110:Caffeine; D013779:Tetrodotoxin; D019284:Thapsigargin; D014700:Verapamil; D013890:Thiourea; D002118:Calcium