Cardiac myocyte excitation by ultrashort high-field pulses

Sufen Wang, Jiexiao Chen, Meng Tse Chen, P. Thomas Vernier, Martin A. Gundersen, Miguel Valderrábano

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

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 Ca 2+ transients in 68/104 cells. Repeating nsPEF increased the likelihood of Ca2+ transient induction (61.8% for <10 nsPEF vs. 80.6% for ≥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 Ca 2+ transients, and ≥20 nsPEF caused normal transients. Ryanodine-thapsigargin and caffeine protected against nsPEF-induced Ca 2+ 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 Ca 2+ in cardiac myocytes by inducing action potentials. Anodal Ca 2+ waves and resistance to Na2+ and Ca2+ channel blockade suggest nonselective ion channel transport via sarcolemmal nanopores as a triggering mechanism.

Original languageEnglish (US)
Pages (from-to)1640-1648
Number of pages9
JournalBiophysical Journal
Volume96
Issue number4
DOIs
StatePublished - Feb 18 2009

ASJC Scopus subject areas

  • Biophysics

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