Fig. 9
Hypothetical model of the multiprotein complex related to the excitation-transcription coupling in skeletal muscle. This model summarizes the findings discussed in this work and in our previous publications [9, 14, 17, 19, 20]. A multiprotein complex is assembled at the beginning of the T-tubule membrane, including dihydropyridine receptor (DHPR, Cav1.1) as the voltage sensor, pannexin 1 (Panx1) as the ATP release channel, the purinergic metabotropic P2Y2 receptor (P2Y2R), and caveolin-3 (Cav3), and dystrophin (Dys) as the scaffold proteins. The membrane depolarization sensed by DHPR induce the ATP release through Panx1. The heterotrimeric G protein attached to P2Y2R sequentially activate, upon ATP binding, phosphoinositide-3 kinase (PI3K) and phospholipase-C (PLC) to produce IP3 and activates calcium release through IP3R, for the slow calcium transient. This IP3-dependent slow calcium transient is involved in the gene expression control of several genes by the excitation-transcription coupling mechanism. The ryanodine receptor-1 (Ryr1), that is known to interact with DHPR, is involved in the excitation-contraction coupling, related with the fast calcium transients, but whether this protein is part of the same multiprotein complex involved in the excitation-transcription coupling has not yet been elucidated