title: Profile of L-type Ca(2+) current and Na(+)/Ca(2+) exchange current during cardiac action potential in ventricular myocytes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacology, University of California, Davis, California 95616, USA.
authors: Tamas
authors: T
authors: Banyasz
authors: Balazs
authors: B
authors: Horvath
authors: Zhong
authors: Z
authors: Jian
authors: Leighton T
authors: LT
authors: Izu
authors: Ye
authors: Y
authors: Chen-Izu
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D020746:Calcium Channels, L-Type / Q000502:physiology*; D006168:Guinea Pigs; D017136:Ion Transport; D032342:Muscle Cells / Q000502:physiology*; D018408:Patch-Clamp Techniques; D019831:Sodium-Calcium Exchanger / Q000502:physiology*; D016276:Ventricular Function / Q000502:physiology*
chemical_list: D020746:Calcium Channels, L-Type; D019831:Sodium-Calcium Exchanger