Figure 2. Conjectural diagram of Mechanically Mediated Crosstalk (MMC) at cellular level.

Figure 2

Conjectural diagram of Mechanically Mediated Crosstalk (MMC) at cellular level. "Stress strain" represents intra and extracellular mechanical input - through extracellular matrix as well, e.g. physiological and biophysical force and pressure changes, including pathophysiological ones e.g. dilated cardiomyopathy, dyskinesia These stress/strains impinge on stretch activated channels (SAC at 12 o'clock), which open to admit charge-carrying ions such as Ca - downward arrow, and Na - curved arrow. Stress/strains activate, diagrammatically, all the moieties on the figurative cell membrane, transmitted via extracellular matrix, integrin & associated focal adhesion kinase (FAK), and the cytoskeleton (designated at 6 o'clock). This stress/strain transmission is indicated clockwise from SAC:- at 1 o'clock - Ion exchangers Na/Ca (electrogenic) & Na/H. Intracellular Na rise will increase intracellular Ca. Further round, at 3 o'clock – translocation (TRANS) of phospholipase C dependent kinase (PKC) to the membrane, embracing1;2 diacylglycerol (DAG) and the (particular) receptor activated C kinase (RACK) bringing it near its designated protein. In this way, hypertrophy, via mitogen activated phosphokinase (MAPK) with tyrosine kinase, and immediate early genes (IEG), encompass PKC. Its translocation to the membrane may also be a contributory mechanism in preconditioning: at 4 o'clock - Phospholipase C (PLC), via phosphotidylinositol (Pi) produces inositol trisphosphate (IP3), and also cleaves the phosphorylated base forming DAG: the former activating Ca2+, and the latter PKC: at 5 o'clock - AT angiotensin, ET endothelin via Gq protein impinges on PLC: at 6 o'clock – integrin & associated focal adhesion kinase (FAK) connect the cytoskeleton with extracellular matrix: at 7 o'clock - L type calcium channel (LCa): at 8 o'clock – 2 pore (tandem pore) forming K channels (2-PK) - still controversial as to the extent they exist in myocardium: at 9 o'clock - ATP activated potassium (KATP) channel: at 11 o'clock – "autonomic" receptors. Acetyl choline (M2) and (β receptors with their respective G proteins Gi & Gs. Here mechanosensitivity of second messengers seem likely, including parts of the cascade in which adenyl cyclase (Ad Cy) splits ATP giving cyclic adenosine monophosphate (cAMP), involving G protein, to affect the LCa channel via phosphokinase A (PKA). Aditionally, ATP can activate the potassium channels, KATP and 2-PK. (See color insert # 8).

From: Mechanically Mediated Crosstalk in Heart

Cover of Mechanosensitivity in Cells and Tissues
Mechanosensitivity in Cells and Tissues.
Kamkin A, Kiseleva I, editors.
Moscow: Academia; 2005.
Copyright © 2005, Academia Publishing House Ltd.

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