OSMOTIC COMPRESSION OF SINGLE CARDIAC MYOCYTES ELIMINATES THE REDUCTION IN CA2-LENGTH( SENSITIVITY OF TENSION AT SHORT SARCOMERE)

According to the Frank-Starling relation, cardiac output varies as a f unction of end-diastolic volume of the ventricle. The cellular basis o f the relation is thought to involve length-dependent variations in Ca 2+ sensitivity of tension; ie, as sarcomere length is increased in car diac muscle, Ca2+ sensitivity of tension also increases. One possible explanation for this effect is that the decrease in myocyte diameter a s 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+ sen sitivity of tension. Single myocytes from rat enzymatically digested v entricles were attached to a force transducer and piezoelectric transl ator, and tension-pCa relations were subsequently characterized at sho rt 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 tensio n (ie, pCa(50)) increased from 5.54+/-0.09 to 5.65+/-0.10 (n=7, mean+/ -SD, P<.001) as SL was increased from approximate to 1.85 to approxima te to 2.25 mu m. 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 (pCa(50), 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 chang es in SL.