Mechanosensitivity as an integrative system in heart: an audit.

This review examines a manifold of apparently loosely linked observations and mechanisms, from membrane to man, and assembles them to support the notion that mechanoelectric transduction is an integrative regulatory system in the heart. For this, the assemblage has to satisfy, at least to some extent, criteria that apply to other integrative regulatory systems such as the endocrine and nervous systems. The integrative effectors in the endocrine system are chemical linkages, circulating hormones: in the nervous system the linkage is a network of cables, nerve conduction and neurotransmitters. Mechanical integration is would be effected through mechanical machinery, cardiac contractile and hydraulic function with attendant stress and strain transmitted via "tensegrity". This can, through the cytoskeleton, begin with membrane integrins and transmit intracellularly for example via F actins to reach the rest of the membranous integrins. Further transmission to the organ is via cell-to-cell adhesion complexes and the extracellular matrix. This tensegrity facilitates integration of force and strain changes from area to area. In consequence, and analogous to the neurendocrine system, mechanoelectric transduction should, and does (1) operate at the molecular or membrane level--this would be via mechanotransducers affecting transmembrane ionic flow; (2) operate in the cell--to influence electrophysiology; (3) have a multicellular expression--e.g. mechanical distortion of one cell can raise intracellular calcium of an adjacent cell; (4) express in the intact organ--e.g. an increase in venous return hydraulically distends the sinoatrial node, steepening its pacemaker potential, thus increasing heart rate. It should also (5) demonstrate elements of a feedback system--"mechanoelectric feedback", and (6) interact with other systems--the cytoskeleton incorporates cell signalling complexes intersecting with other signal cascades. Finally, (7) it can malfunction to produce clinical abnormality--it contributes electrophysiologically to lethal cardiac arrhythmia. This anatomical and functional behaviour of mechanoelectric transduction could sanction the prospect of viewing it as analogous to the other integrative physiological systems.