Abstract
We present a model for predicting the temporal and spatial dependence
of Ca in the cardiac subsarcolemmal diadic region (cleft), following
Ca release from the "feet" of the sarcoplasmic reticulum. This region
is modeled as a disc 10 nm thick, 430 nm in radius, with or without
Ca binding sites and open at its periphery to the cytosol. Ca is
computed for three diffusion coefficients (100, 20 and 4\% of aqueous
diffusion), following release of a 20-msec square pulse sufficient
to produce 50\% maximal contractile force, or repetitive release
(400/min) of such pulses. Numerical solutions are obtained for the
general diffusion/binding problem and analytic solutions for the
case of no binding sites. For the middle value of diffusion coefficient,
and in the absence of binding sites, Ca rises to approximately
1.5 mM in 20-msec and then falls to approximately 0.1 microM in less
than 3 msec. Adding binding sites reduces peak Ca to approximately
0.6 mM but prolongs its decline, requiring approximately 200 msec
to reach 20 microM. For repetitive release Ca is greater than 100
microM for roughly half of each cycle. Two major implications of
the predicted Ca are: (i) The effect of Ca binding sites on Ca
will cause Ca efflux from the cleft via the Na-Ca exchanger (Km(Ca)
approximately 20 microM) to continue at a significant level for greater
than 200 msec. (ii) The time constant for inactivation of release
from the "feet" must be much greater than for activation if Ca-induced
Ca release is to continue for greater than 1-2 msec.
- 1404341
- animals,
- binding
- calcium,
- cell
- cells,
- compartmentation,
- cultured,
- gov't,
- lanthanum,
- m,
- models,
- myocardium,
- newborn,
- nifedipine,
- non-u.s.
- p.h.s.,
- rats,
- research
- reticulu,
- ryanodine,
- sarcolemma,
- sarcoplasmic
- sites,
- support,
- terpenes,
- thapsigargin,
- theoretical,
- u.s.
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