MicroRNA: a toolkit fine-tuning the dyadic "fuzzy space"?

Abstract

Cardiac excitation-contraction (E-C) coupling links action potentials to muscle contraction and is in essence a process of calcium ion mobilization. The central mechanism governing this process in ventricular myocytes is Ca²⁺- induced Ca²⁺ release, or CICR. It has been established for more than 20 years that CICR operates in a local control mode, taking place in a restricted junctional space of ≈ 12 to 15 nm between the transverse (T)-tubule and sarcoplasmic reticulum (SR) membranes, namely, the junctional membrane complexes or cardiac dyads.^, Within this dyadic “fuzzy space,” clusters of ryanodine receptor (RyR) Ca²⁺ release channels on the SR constitute the calcium release apparatus together with the directly apposed voltage-gated L-type Ca²⁺ channels (LTCCs) located primarily on the T-tubule membrane. On membrane depolarization, a small amount of Ca²⁺ influx through the opening of LTCCs locally activates adjacent RyRs to release a much larger (≈10 times) amount of Ca²⁺ from the SR.^, The normal, functional cross-talk between LTCCs and RyRs depends on a stable local ultrastructure— the cardiac dyad.