Na$^+$-Ca$^2+$ exchange (NCX) is crucial in the regulation
of Ca$^2+$(i) and cardiac contractility, but key details of
its dynamic function during the heartbeat are not known. In the present
study, we assess how NCX current (I(NCX)) varies during a rabbit
ventricular action potential (AP). First, we measured the steady-state
voltage and Ca$^2+$(i) dependence of I(NCX) under conditions
when Ca$^2+$(i) was heavily buffered. We then used this relationship
to infer the submembrane Ca$^2+$(i) (Ca$^2+$(sm)) sensed
by NCX during a normal AP and Ca$^2+$(i) transient (when the
AP was interrupted to produce an I(NCX) tail current). The Ca$^2+$(i)
dependence of I(NCX) at -90 mV allowed us to convert the peak inward
I(NCX) tail currents to Ca$^2+$(sm). Peak Ca$^2+$(sm)
measured via this technique was >3.2 micromol/L within < 32 ms of
the AP upstroke (versus peak Ca$^2+$(i) of 1.1 micromol/L at
81 ms measured with the global Ca$^2+$ indicator indo-1). The
voltage and Ca$^2+$(sm) dependence of I(NCX) allowed us to
infer I(NCX) during the normal AP and Ca$^2+$ transient. The
early rise in Ca$^2+$(sm) causes I(NCX) to be inward for the
majority of the AP. Thus, little Ca$^2+$ influx via NCX is expected
under physiological conditions, but this can differ among species
and in pathophysiological conditions.
%0 Journal Article
%1 Webe_2002_182
%A Weber, Christopher R
%A Piacentino, Valentino
%A Ginsburg, Kenneth S
%A Houser, Steven R
%A Bers, Donald M
%D 2002
%J Circ. Res.
%K 11834700 ATPase, Action Adenocarcinoma, Adult, Allosteric Animal, Animals, Blockers, Calcium, Cell Cells, Channel Channels, Congestive, Contraction, Diastole, Disease Electric Electrophysiology, Esophageal Exchanger, Failure, Fatal Fluid, Gov't, Guinea Heart Heart, Humans, In Intracellular Ion Kinetics, Male, Maxillary Membrane Membrane, Models, Muscle Myocardial Myocardium, Neoplasms, Nickel, Non-U.S. Outcome, P.H.S., Patch-Clamp Pigs, Potentia, Potentials, Rabbits, Re, Regulation, Research Reticulum, Sarcoplasmic Separation, So, Sodium Sodium, Sodium-Calcium Stimulation, Strophanthidin, Support, Techniques, Tetrodotoxin, Transport, U.S. Ventricles, Vitro, dium-Calcium ls, search {N}a$^{+}$-{K}$^{+}$-Exchanging
%N 2
%P 182--189
%T Na$^+$-Ca$^2+$ exchange current and submembrane Ca$^2+$
during the cardiac action potential.
%U http://circres.ahajournals.org/cgi/content/full/90/2/182
%V 90
%X Na$^+$-Ca$^2+$ exchange (NCX) is crucial in the regulation
of Ca$^2+$(i) and cardiac contractility, but key details of
its dynamic function during the heartbeat are not known. In the present
study, we assess how NCX current (I(NCX)) varies during a rabbit
ventricular action potential (AP). First, we measured the steady-state
voltage and Ca$^2+$(i) dependence of I(NCX) under conditions
when Ca$^2+$(i) was heavily buffered. We then used this relationship
to infer the submembrane Ca$^2+$(i) (Ca$^2+$(sm)) sensed
by NCX during a normal AP and Ca$^2+$(i) transient (when the
AP was interrupted to produce an I(NCX) tail current). The Ca$^2+$(i)
dependence of I(NCX) at -90 mV allowed us to convert the peak inward
I(NCX) tail currents to Ca$^2+$(sm). Peak Ca$^2+$(sm)
measured via this technique was >3.2 micromol/L within < 32 ms of
the AP upstroke (versus peak Ca$^2+$(i) of 1.1 micromol/L at
81 ms measured with the global Ca$^2+$ indicator indo-1). The
voltage and Ca$^2+$(sm) dependence of I(NCX) allowed us to
infer I(NCX) during the normal AP and Ca$^2+$ transient. The
early rise in Ca$^2+$(sm) causes I(NCX) to be inward for the
majority of the AP. Thus, little Ca$^2+$ influx via NCX is expected
under physiological conditions, but this can differ among species
and in pathophysiological conditions.
@article{Webe_2002_182,
abstract = {{N}a$^{+}$-{C}a$^{2+}$ exchange (NCX) is crucial in the regulation
of [{C}a$^{2+}$](i) and cardiac contractility, but key details of
its dynamic function during the heartbeat are not known. In the present
study, we assess how NCX current (I(NCX)) varies during a rabbit
ventricular action potential (AP). First, we measured the steady-state
voltage and [{C}a$^{2+}$](i) dependence of I(NCX) under conditions
when [{C}a$^{2+}$](i) was heavily buffered. We then used this relationship
to infer the submembrane [{C}a$^{2+}$](i) ([{C}a$^{2+}$](sm)) sensed
by NCX during a normal AP and [{C}a$^{2+}$](i) transient (when the
AP was interrupted to produce an I(NCX) tail current). The [{C}a$^{2+}$](i)
dependence of I(NCX) at -90 mV allowed us to convert the peak inward
I(NCX) tail currents to [{C}a$^{2+}$](sm). Peak [{C}a$^{2+}$](sm)
measured via this technique was >3.2 micromol/L within < 32 ms of
the AP upstroke (versus peak [{C}a$^{2+}$](i) of 1.1 micromol/L at
81 ms measured with the global {C}a$^{2+}$ indicator indo-1). The
voltage and [{C}a$^{2+}$](sm) dependence of I(NCX) allowed us to
infer I(NCX) during the normal AP and {C}a$^{2+}$ transient. The
early rise in [{C}a$^{2+}$](sm) causes I(NCX) to be inward for the
majority of the AP. Thus, little {C}a$^{2+}$ influx via NCX is expected
under physiological conditions, but this can differ among species
and in pathophysiological conditions.},
added-at = {2009-06-03T11:20:58.000+0200},
author = {Weber, Christopher R and Piacentino, Valentino and Ginsburg, Kenneth S and Houser, Steven R and Bers, Donald M},
biburl = {https://www.bibsonomy.org/bibtex/2846a6b89468e1cab89d34423c613fdee/hake},
description = {The whole bibliography file I use.},
file = {Webe_2002_182.pdf:Webe_2002_182.pdf:PDF},
interhash = {ef429b3940a2db63313f07d69ee55fae},
intrahash = {846a6b89468e1cab89d34423c613fdee},
journal = {Circ. Res.},
key = 151,
keywords = {11834700 ATPase, Action Adenocarcinoma, Adult, Allosteric Animal, Animals, Blockers, Calcium, Cell Cells, Channel Channels, Congestive, Contraction, Diastole, Disease Electric Electrophysiology, Esophageal Exchanger, Failure, Fatal Fluid, Gov't, Guinea Heart Heart, Humans, In Intracellular Ion Kinetics, Male, Maxillary Membrane Membrane, Models, Muscle Myocardial Myocardium, Neoplasms, Nickel, Non-U.S. Outcome, P.H.S., Patch-Clamp Pigs, Potentia, Potentials, Rabbits, Re, Regulation, Research Reticulum, Sarcoplasmic Separation, So, Sodium Sodium, Sodium-Calcium Stimulation, Strophanthidin, Support, Techniques, Tetrodotoxin, Transport, U.S. Ventricles, Vitro, dium-Calcium ls, search {N}a$^{+}$-{K}$^{+}$-Exchanging},
month = Feb,
number = 2,
pages = {182--189},
pmid = {11834700},
timestamp = {2009-06-03T11:21:37.000+0200},
title = {{N}a$^{+}$-{C}a$^{2+}$ exchange current and submembrane [{C}a$^{2+}$]
during the cardiac action potential.},
url = {http://circres.ahajournals.org/cgi/content/full/90/2/182},
volume = 90,
year = 2002
}