Abstract
1. The purpose of this study was to determine whether mechanisms other
than Ca$^2+$ influx via L-type Ca$^2+$ current (ICa) might
contribute to activation of contraction in rat ventricular myocytes.
The whole-cell voltage-clamp technique was used with normal transmembrane
K$^+$ and Na$^+$ gradients at 34 degrees C. The sarcoplasmic
reticulum (SR) was conditioned with one to three prepulses to +100
mV for 100 ms. 2. Cell shortening (delta L) increased with test voltage
up to a plateau level at about +20 mV, beyond which cell shortening
remained fairly constant, thus describing a sigmoidal voltage dependence.
This relationship was obtained when holding potential (Vh) was either
-40 or -70 mV; however, greater shortening was obtained at the more
negative Vh. 3. The sigmoidal V-delta L relationship was converted
to a bell shape following the magnitude of ICa when internal Cs+
was substituted for K$^+$ and when the temperature was reduced
to 22 degrees C. 4. At 34 degrees C, block of ICa with nifedipine
(10 microM) decreased shortening by about 50\% but did not alter
the voltage dependence of delta L when Vh was either -40 or -70 mV.
Addition of Ni2+ (4-5 mM) blocked all remaining contractions. 5.
When cell shortening was triggered by an action potential voltage
clamp, there was again about 50\% of the contraction that was insensitive
to nifedipine but was blocked by Ni2+. 6. Our results demonstrate
that there is a significant contribution of a nifedipine-insensitive
mechanism to the activation of contraction. This mechanism is likely
to be reverse mode Na$^+$-Ca$^2+$ exchange since it appears
to be sensitive to both voltage and Ni2+. We conclude that a contribution
of reverse Na$^+$-Ca$^2+$ exchange to activation of excitation-contraction
coupling occurs in rat heart at near-physiological conditions which
include warm temperatures, normal transmembrane Na$^+$ and K$^+$
gradients and activation in response to an action potential.
- 8782114
- action
- animals,
- blockers,
- calcium
- calcium,
- cats,
- cesium,
- channel
- channels,
- contraction,
- electrophysiology,
- factors,
- function,
- gov't,
- heart
- heart,
- humans,
- in
- infant,
- myocardial
- myocardium,
- nifedipine,
- non-u.s.
- p.h.s.,
- patch-clamp
- potassium,
- potentials,
- rats,
- research
- reticulum,
- ryanodine,
- sarcoplasmic
- saxitoxin,
- sodium
- sodium,
- sprague-dawley,
- support,
- techniques,
- temperature,
- time
- u.s.
- ventricles,
- ventricular
- vitro,
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