Profile of L-type Ca 2+ current and Na +/Ca 2+ exchange current during cardiac action potential in ventricular myocytes

Tamas Banyasz, Balazs Horvath, Zhong Jian, Leighton T Izu, Ye Chen-Izu

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

The L-type Ca 2+ current (I Ca,L) and the Na +/Ca 2+ exchange current (I NCX) are major inward currents that shape the cardiac action potential (AP). Previously, the profile of these currents during the AP was determined from voltage-clamp experiments that used Ca 2+ buffer. In this study, we aimed to obtain direct experimental measurement of these currents during cardiac AP with Ca 2+ cycling. A newly developed AP-clamp sequential dissection method was used to record ionic currents in guinea pig ventricular myocytes under a triad of conditions: using the cell's own AP as the voltage command, using internal and external solutions that mimic the cell's ionic composition, and, importantly, not using any exogenous Ca 2+ buffer. The nifedipine-sensitive current (I NIFE), which is composed of I Ca,L and I NCX, revealed hitherto unreported features during the AP with Ca 2+ cycling in the cell. We identified 2 peaks in the current profile followed by a long residual current extending beyond the AP, coinciding with a residual depolarization. The second peak and the residual current become apparent only when Ca 2+ is not buffered. Pharmacological dissection of I NIFE by using SEA0400 shows that I Ca,L is dominant during phases 1 and 2 whereas I NCX contributes significantly to the inward current during phases 3 and 4 of the AP. These data provide the first direct experimental visualization of I Ca,L and I NCX during cardiac the AP and Ca 2+ cycle. The residual current reported here can serve as a potential substrate for afterdepolarizations when increased under pathologic conditions.

Original languageEnglish (US)
Pages (from-to)134-142
Number of pages9
JournalHeart Rhythm
Volume9
Issue number1
DOIs
StatePublished - Jan 2012

Keywords

  • Action potential
  • Arrhythmia
  • Cardiac Ventricular
  • L-type Ca channel
  • Myocyte
  • Na /Ca exchanger

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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