English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

H(+) ions are powerful modulators of cardiac function, liberated during metabolic activity. Among their physiological effects is a chemical gating of cell-to-cell communication, caused by H(+)-mediated closure of connexin (Cx) channels at gap junctions. This protects surrounding tissue from the damaging effects of local intracellular acidosis. Cx proteins (largely Cx-43 in ventricle) form multimeric pores between cells, permitting translocation of ions and other solutes up to approximately 1 kDa. The channels are essential for electrical and metabolic coordination of a tissue. Here we demonstrate that, contrary to expectation, H(+) ions can induce an increase of gap-junctional permeability. This occurs during modest intracellular acid loads in myocyte pairs isolated from mammalian ventricle. We show that the increase in permeability allows a local rise of [H(+)](i) to dissipate into neighboring myocytes, thereby providing a mechanism for spatially regulating intracellular pH (pH(i)). During larger acid loads, the increased permeability is overridden by a more familiar H(+)-dependent inhibition (H(+) inactivation). This restricts cell-to-cell H(+) movement, while allowing sarcolemmal H(+) transporters such as Na(+)/H(+) exchange, to extrude the acid from the cell. The H(+) sensitivity of Cx channels therefore defines whether junctional or sarcolemmal mechanisms are selected locally for the removal of an acid load. The bell-shaped pH dependence of permeability suggests that, in addition to H(+) inactivation, an H(+) activation process regulates the ensemble of Cx channels open at the junction. As well as promoting spatial pH(i) regulation, H(+) activation of junctional permeability may link increased metabolic activity to improved myocardial coupling, the better to meet mechanical demand.

H + Ion Activation and Inactivation of the Ventricular Gap Junction

H ⁺ Ion Activation and Inactivation of the Ventricular Gap Junction