A shortcut to a skeletal muscle DHPR knock-in?

摘要

Excitation-contraction (EC) coupling in mammalian skeletal muscle relies on intermolecular communication between the L-type Ca2+ channel (or 1,4-dihydropyridine receptor; DHPR) and the type 1 ryanodine receptor (RyRl). Conformational rearrangements in the DHPR that occur in response to transverse tubular membrane depolarization are transduced to RyRl via a physical coupling between the two channels that is largely independent of any Ca2+ entry via the DHPR (reviewed in Karunasekara et til 2009). In addition to this 'orthograde' signal transmitted from the DHPR to RyRl, conformational coupling also supports a 'retrograde' signal from RyRl to the DHPR which increases macroscopic L-type current amplitude (Nakai et ah 1996).