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 language | English (US) |
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Pages (from-to) | 134-142 |
Number of pages | 9 |
Journal | Heart Rhythm |
Volume | 9 |
Issue number | 1 |
DOIs | |
State | Published - 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)