학술논문

Voltage-gated Ca2+ influx through L-type channels contributes to sarcoplasmic reticulum Ca2+ loading in skeletal muscle
Document Type
Academic Journal
Source
Journal of Physiology. Nov 01, 2015 593(21):4781-4797
Subject
Language
English
ISSN
0022-3751
Abstract
Muscle contraction is triggered by Ca ions released from the sarcoplasmic reticulum (SR) in response to depolarization of skeletal muscle fibres. Muscle activation is also associated with a voltage-activated trans-sarcolemmal Ca influx early identified as a current flowing through L-type Ca channels. Because removal of external Ca does not impede fibres from contracting, a negligible role was given to this voltage-activated Ca entry, although the decline of Ca release is more pronounced in the absence of Ca during long-lasting activation. Furthermore, it is not clearly established whether Ca exclusively flows through L-type channels or in addition through a parallel voltage-activated pathway distinct from L-type channels. Here, by monitoring the quenching of fura-2 fluorescence resulting from Mn influx in voltage-controlled mouse and zebrafish isolated muscle fibres, we show that the L-type current is the only contributor to Ca influx during long-lasting depolarizations in skeletal muscle. Calibration of the Mn quenching signal allowed us to estimate a mean Mn current of 0.31 ± 0.06 A F flowing through L-type channels during a train of action potentials. Measurements of SR Ca changes with fluo-5N in response to depolarization revealed that an elevated voltage-activated Ca current potentiated SR Ca loading and addition of external Mn produced quenching of fluo-5N in the SR, indicating that voltage-activated Ca/Mn influx contributes to SR Ca/Mn loading.(Figure is included in full-text article.)