Abstract
To determine features of the steady state Ca$^2+$-tension relationship
in intact heart, we measured steady force and intracellular Ca$^2+$
(Ca$^2+$i) in tetanized ferret papillary muscles. Ca$^2+$i
was estimated from the luminescence emitted by muscles that had been
microinjected with aequorin, a Ca$^2+$-sensitive, bioluminescent
protein. We found that by raising extracellular Ca$^2+$ and/or
by exposing muscles to the Ca$^2+$ channel agonist Bay K 8644,
tension development could be varied from rest to an apparently saturating
level, at which increases in Ca$^2+$i produced no further rise
in force. 95\% of maximal Ca$^2+$-activated force was reached
at a Ca$^2+$i of 0.85 +/- 0.06 microM (mean +/- SEM; n = 7),
which suggests that the sensitivity of the myofilaments to Ca$^2+$i
is far greater than anticipated from studies of skinned heart preparations
(or from previous studies using Ca$^2+$-sensitive microelectrodes
in intact heart). Our finding that maximal force was reached by approximately
1 microM also allowed us to calculate that the steady state Ca$^2+$i-tension
relationship, as it might be observed in intact muscle, should be
steep (Hill coefficient of greater than 4), which is consistent with
the Hill coefficient estimated from the entire Ca$^2+$i-tension
relationship derived from families of variably activated tetani (6.08
+/- 0.68; n = 7). Finally, with regard to whether steady state measurements
can be applied directly toward understanding physiological contractions,
we found that the relation between steady force and Ca$^2+$i
obtained during tetani was steeper than that between peak force and
peak Ca$^2+$i observed during physiological twitches.
- 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-,
- 2419483
- 3-pyridinecarboxylic
- acid,
- animals,
- calcium,
- carnivora,
- channels,
- chemical,
- contraction,
- ester,
- ferrets,
- gov't,
- heart,
- in
- ion
- membrane
- methyl
- muscles,
- myocardial
- nifedipine,
- non-u.s.
- p.h.s.,
- papillary
- perfusion,
- potentials,
- research
- ryanodine,
- stimulation,
- support,
- u.s.
- vitro,
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