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

Mechanical alternans in cardiac muscle is associated with intracellular Ca(2+) alternans. Mechanisms underlying intracellular Ca(2+) alternans are unclear. In previous experimental studies, we produced alternans of systolic Ca(2+) under voltage clamp, either by partially inhibiting the Ca(2+) release mechanism, or by applying small depolarizing pulses. In each case, alternans relied on propagating waves of Ca(2+) release. The aim of this study is to investigate by computer modeling how alternans of systolic Ca(2+) is produced. A mathematical model of a cardiac cell with 75 coupled elements is developed, with each element contains L-type Ca(2+) current, a subspace into which Ca release takes place, a cytoplasmic space, sarcoplasmic reticulum (SR) release channels [ryanodine receptor (RyR)], and uptake sites (SERCA). Interelement coupling is via Ca(2+) diffusion between neighboring subspaces via cytoplasmic spaces and network SR spaces. Small depolarizing pulses were simulated by step changes of cell membrane potential (20 mV) with random block of L-type channels. Partial inhibition of the release mechanism is mimicked by applying a reduction of RyR open probability in response to full stimulation by L-type channels. In both cases, systolic alternans follow, consistent with our experimental observations, being generated by propagating waves of Ca(2+) release and sustained through alternation of SR Ca(2+) content. This study provides novel and fundamental insights to understand mechanisms that may underlie intracellular Ca(2+) alternans without the need for refractoriness of L-type Ca or RyR channels under rapid pacing.

Alternans of cardiac calcium cycling in a cluster of ryanodine receptors: a simulation study