Role of the Giant Elastic Protein Titin in the Frank-Starling Mechanism of the Heart

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Abstract:

Increased ventricular volume enhances the systolic performance, a phenomenon known as Frank-Starling's law of the heart. At its basis is the ability of cardiac muscle to produce increased active force in response to increased muscle length. Although numerous studies have been conducted to elucidate the molecular basis of length-dependent activation, the mechanism remains elusive. The giant protein titin (also known as connectin) is the third filament system in the sarcomere and is responsible for most passive stiffness of striated muscle in the physiological sarcomere length range. The force generated by titin is usually seen as passive and independent of active force generation. Recent findings, however, suggest that titin-based passive force modulates actin-myosin interaction, resulting in greater active force in response to stretch. In this short review, we discuss the molecular mechanisms of length-dependent activation, focusing on the possible role of titin in its regulation.

Keywords: cardiac muscle; frank-starling; heart; sarcomere length; titin

Document Type: Review Article

DOI: http://dx.doi.org/10.2174/1570161043476357

Affiliations: Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, WA 99164-6520, USA.

Publication date: April 1, 2004

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  • Vascular disease is the commonest cause of death in Westernized countries and its incidence is on the increase in developing countries. It follows that considerable research is directed at establishing effective treatment for acute vascular events. Long-term treatment has also received considerable attention (e.g. for symptomatic relief). Furthermore, effective prevention, whether primary or secondary, is backed by the findings of several landmark trials.

    Vascular disease is a complex field with primary care physicians and nurse practitioners as well as several specialties involved. The latter include cardiology, vascular and cardio thoracic surgery, general medicine, radiology, clinical pharmacology and neurology (stroke units). Current Vascular Pharmacology will publish reviews to update all those concerned with the treatment of vascular disease. For example, reviews commenting on recently published trials or new drugs will be included. In addition to clinically relevant topics we will consider 'research-based' reviews dealing with future developments and potential drug targets. Therefore, another function of Current Vascular Pharmacology is to bridge the gap between clinical practice and ongoing research.

    Debates will also be encouraged in the correspondence section of this journal.
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