Is titin the length sensor in cardiac muscle? Physiological and physiopathological perspectives.
One of the most salient physiological characteristics of cardiac muscle is that a dilated heart pumps more vigorously, a phenomenon known as the Frank-Starling relationship (see Allen and Kentish, 1985). At least two cellular mechanisms participate in this phenomenon: the reduction of the interfilament lattice spacing which favors the formation of cross-bridges (Wang and Fuchs, 1995) and the increased affinity of troponin C (TnC) for calcium (Ca2+) (Babu et al., 1988). In the latter case, it has been established that TnC itself is not the length sensor (Moss et al., 1991). The intracellular structure(s) able to sense changes in cell length has always been challenged and is still not known. We previously observed on intact isolated cardiac cells that active tension is more closely related to passive tension than to sarcomere length per se (Cazorla et al., 1997). This might have some physiological implications in the working heart since we found that sub-epicardial cells are more supple than sub-endocardial cells. In the present work on skinned cells, we studied the relationship between different levels of passive tension (modulated by a mild trypsin digestion) and the shift in pCa50 of tension-pCa relations induced by a stretch of cells from 1.9 to 2.3 microns sarcomere length. A significant correlation was obtained between passive tension and the stretch-induced shift in pCa50, or stretch-sensitivity of the active force. These observations led us to assume that titin might play a role in sensing cell length to modulate the contractile activity. Besides, it is known that myocardial infarcted cells are less sensitive to stretch. We propose that, in such a rat model, alterations of titin might participate in heart failure.
Le Guennec
J Y
JY
Laboratoire de Physiologie des Cellules Cardiaques et Vasculaires, Tours, France.
Cazorla
O
O
Lacampagne
A
A
Vassort
G
G
D000818:Animals; D002478:Cells, Cultured; D064211:Connectin; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D009124:Muscle Proteins / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000648:ultrastructure; D011494:Protein Kinases / Q000502:physiology*; D051381:Rats; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure
D064211:Connectin; D009124:Muscle Proteins; D011494:Protein Kinases