Abstract
Sodium overload of cardiac cells can accompany various pathologies
and induce fatal cardiac arrhythmias. We investigate effects of elevated
intracellular sodium on the cardiac action potential (AP) and on
intracellular calcium using the Luo-Rudy model of a mammalian ventricular
myocyte. The results are: 1) During rapid pacing, AP duration (APD)
shortens in two phases, a rapid phase without Na$^+$ accumulation
and a slower phase that depends on Na$^+$(i). 2) The rapid
APD shortening is due to incomplete deactivation (accumulation)
of I(Ks). 3) The slow phase is due to increased repolarizing currents
I(NaK) and reverse-mode I(NaCa), secondary to elevated Na$^+$(i).
4) Na$^+$-overload slows the rate of AP depolarization, allowing
time for greater I(Ca(L)) activation; it also enhances reverse-mode
I(NaCa). The resulting increased Ca$^2+$ influx triggers a greater
Ca$^2+$(i) transient. 5) Reverse-mode I(NaCa) alone can trigger
Ca$^2+$ release in a voltage and Na$^+$(i)-dependent manner.
6) During I(NaK) block, Na$^+$ and Ca$^2+$ accumulate and
APD shortens due to enhanced reverse-mode I(NaCa); contribution
of I(K(Na)) to APD shortening is negligible. By slowing AP depolarization
(hence velocity) and shortening APD, Na$^+$-overload acts to
enhance inducibility of reentrant arrhythmias. Shortened APD with
elevated Ca$^2+$(i) (secondary to Na$^+$-overload) also
predisposes the myocardium to arrhythmogenic delayed afterdepolarizations.
- 10777735
- action
- animals,
- arrhythmia,
- atpase,
- biophysics,
- calcium
- calcium,
- cardiovascular,
- contraction,
- gov't,
- guinea
- in
- ion
- models,
- myocardial
- myocardium,
- non-u.s.
- p.h.s.,
- pigs,
- potassium,
- potentials,
- research
- reticulum,
- sarcoplasmic
- signaling,
- sodium,
- support,
- transport,
- u.s.
- vitro,
- {n}a$^{+}$-{k}$^{+}$-exchanging
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