Abstract
Cardiac contractility is regulated by changes in intracellular Ca concentration ([Ca2+]i). Normal function
requires that [Ca2+]i be sufficiently high in systole and low in diastole. Much of the Ca needed for contraction comes
from the sarcoplasmic reticulum and is released by the process of calcium-induced calcium release. The factors that
regulate and fine-tune the initiation and termination of release are reviewed. The precise control of intracellular
Ca cycling depends on the relationships between the various channels and pumps that are involved. We consider 2
aspects: (1) structural coupling: the transporters are organized within the dyad, linking the transverse tubule and
sarcoplasmic reticulum and ensuring close proximity of Ca entry to sites of release. (2) Functional coupling: where the
fluxes across all membranes must be balanced such that, in the steady state, Ca influx equals Ca efflux on every beat.
The remainder of the review considers specific aspects of Ca signaling, including the role of Ca buffers, mitochondria,
Ca leak, and regulation of diastolic [Ca2+]i. (Circ Res. 2017;121:00-00. DOI: 10.1161/CIRCRESAHA.117.310230.)
requires that [Ca2+]i be sufficiently high in systole and low in diastole. Much of the Ca needed for contraction comes
from the sarcoplasmic reticulum and is released by the process of calcium-induced calcium release. The factors that
regulate and fine-tune the initiation and termination of release are reviewed. The precise control of intracellular
Ca cycling depends on the relationships between the various channels and pumps that are involved. We consider 2
aspects: (1) structural coupling: the transporters are organized within the dyad, linking the transverse tubule and
sarcoplasmic reticulum and ensuring close proximity of Ca entry to sites of release. (2) Functional coupling: where the
fluxes across all membranes must be balanced such that, in the steady state, Ca influx equals Ca efflux on every beat.
The remainder of the review considers specific aspects of Ca signaling, including the role of Ca buffers, mitochondria,
Ca leak, and regulation of diastolic [Ca2+]i. (Circ Res. 2017;121:00-00. DOI: 10.1161/CIRCRESAHA.117.310230.)
| Original language | English |
|---|---|
| Journal | Circulation research |
| DOIs | |
| Publication status | Published - 6 Jul 2017 |