Articles |
From the Department of Physiology, University of Wisconsin Medical School, Madison.
Correspondence to Kerry S. McDonald, PhD, Department of Physiology, University of Wisconsin, School of Medicine, 1300 University Ave, Madison, WI 53706.
Abstract According to the Frank-Starling relation, cardiac
output varies as a function of end-diastolic volume of the
ventricle. The cellular basis of the relation is thought to involve
length-dependent variations in Ca2+ sensitivity of
tension; ie, as sarcomere length is increased in cardiac muscle,
Ca2+ sensitivity of tension also increases. One
possible explanation for this effect is that the decrease in myocyte
diameter as muscle length is increased reduces the lateral spacing
between thick and thin filaments, thereby increasing the likelihood of
cross-bridge interaction with actin. To examine this idea, we measured
the effects of osmotic compression of single skinned cardiac myocytes
on Ca2+ sensitivity of tension. Single myocytes from
rat enzymatically digested ventricles were attached to a force
transducer and piezoelectric translator, and tension-pCa relations were
subsequently characterized at short sarcomere length (SL), at the same
short SL in the presence of 2.5% dextran, and at long SL. The pCa
(-log[Ca2+]) for half-maximal tension (ie,
pCa50) increased from 5.54±0.09 to 5.65±0.10 (n=7,
mean±SD, P<.001) as SL was increased from
1.85 to
2.25 µm. Osmotic compression of myocytes at short length also
increased Ca2+ sensitivity of tension, shifting
tension-pCa relations to [Ca2+] levels similar to
those observed at long length (pCa50, 5.68±0.11).
These results support the idea that the length dependence of
Ca2+ sensitivity of tension in cardiac muscle arises
in large part from the changes in interfilament lattice spacing that
accompany changes in SL.
Key Words: Ca2+ sensitivity cardiac myocytes isometric contraction
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