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) |
|---|---|
| Pages (from-to) | 134-142 |
| Number of pages | 9 |
| Journal | Heart Rhythm |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2012 |
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Keywords
- Action potential
- Arrhythmia
- Cardiac Ventricular
- L-type Ca channel
- Myocyte
- Na /Ca exchanger
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology (medical)
Cite this
Profile of L-type Ca 2+ current and Na +/Ca 2+ exchange current during cardiac action potential in ventricular myocytes. / Banyasz, Tamas; Horvath, Balazs; Jian, Zhong; Izu, Leighton T; Chen-Izu, Ye.
In: Heart Rhythm, Vol. 9, No. 1, 01.2012, p. 134-142.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Profile of L-type Ca 2+ current and Na +/Ca 2+ exchange current during cardiac action potential in ventricular myocytes
AU - Banyasz, Tamas
AU - Horvath, Balazs
AU - Jian, Zhong
AU - Izu, Leighton T
AU - Chen-Izu, Ye
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - Action potential
KW - Arrhythmia
KW - Cardiac Ventricular
KW - L-type Ca channel
KW - Myocyte
KW - Na /Ca exchanger
UR - http://www.scopus.com/inward/record.url?scp=84555190595&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84555190595&partnerID=8YFLogxK
U2 - 10.1016/j.hrthm.2011.08.029
DO - 10.1016/j.hrthm.2011.08.029
M3 - Article
C2 - 21884673
AN - SCOPUS:84555190595
VL - 9
SP - 134
EP - 142
JO - Heart Rhythm
JF - Heart Rhythm
SN - 1547-5271
IS - 1
ER -