title: Titin-based regulations of diastolic and systolic functions of mammalian cardiac muscle.
abstract: Titin is the largest protein in mammals; it forms an elastic filament along the myofibril of cardiac and skeletal muscles. Novel studies employing the recently available varied technologies have revealed the molecular mechanisms by which titin generates passive force in the sarcomere in response to external stretch. Changes in titin stiffness occur during heart disease via a shift in the expression ratio of the two main titin isoforms, called N2B (stiff type) and N2BA (compliant type) titins. Protein kinase (PK)A, PKG and PKC phosphorylate the cardiac specific I-band titin segment, resulting in an acute decrease (by PKA and PKG) or increase (by PKC) in passive force. It has also been discovered that titin performs roles that go beyond passive force generation, by enhancing or terminating active force production, thereby adjusting the Frank-Starling mechanism of the heart. Therefore, titin is a self-adjustable and multi-functional spring that is indispensable for proper heart functions. Here, we discuss how titin regulates the passive and active properties of cardiac muscle in normal physiological conditions as well as in chronic heart disease.
authors: Department of Cell Physiology, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan. noriof@jikei.ac.jp
authors: Norio
authors: N
authors: Fukuda
authors: Takako
authors: T
authors: Terui
authors: Shin'ichi
authors: S
authors: Ishiwata
authors: Satoshi
authors: S
authors: Kurihara
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D064211:Connectin; D003971:Diastole / Q000502:physiology*; D006801:Humans; D008954:Models, Biological; D009124:Muscle Proteins / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D013599:Systole / Q000502:physiology*
chemical_list: D064211:Connectin; D009124:Muscle Proteins; C577285:TTN protein, human; D011494:Protein Kinases; D002118:Calcium