Pannexin 1 channels in skeletal muscles

Abstract

Normal myotubes and adult innervated skeletal myofibers express the glycoprotein pannexin1 (Panx1). Six of them form a “gap junction hemichannel-like” structure that connects the cytoplasm with the extracellular space; here they will be called Panx1 channels. These are poorly selective channels permeable to ions, small metabolic substrate, and signaling molecules. So far little is known about the role of Panx1 channels in muscles but skeletal muscles of Panx1−/− mice do not show an evident phenotype. Innervated adult fast and slow skeletal myofibers show Panx1 reactivity in close proximity to dihydropyridine receptors in the sarcolemma of T-tubules. These Panx1 channels are activated by electrical stimulation and extracellular ATP. Panx1 channels play a relevant role in potentiation of muscle contraction because they allow release of ATP and uptake of glucose, two molecules required for this response. In support of this notion, the absence of Panx1 abrogates the potentiation of muscle contraction elicited by repetitive electrical stimulation, which is reversed by exogenously applied ATP. Phosphorylation of Panx1 Thr and Ser residues might be involved in Panx1 channel activation since it is enhanced during potentiation of muscle contraction. Under denervation, Panx1 levels are upregulated and this partially explains the reduction in electrochemical gradient, however its absence does not prevent denervation-induced atrophy but prevents the higher oxidative state. Panx1 also forms functional channels at the cell surface of myotubes and their functional state has been associated with intracellular Ca2+ signals and regulation of myotube plasticity evoked by electrical stimulation. We proposed that Panx1 channels participate as ATP channels and help to keep a normal oxidative state in skeletal muscles.

Regulation of pannexin and connexin channels and their functional role in skeletal muscles

“…In support to these proposed roles of Panx1 HC-mediated ATP release, it has been shown that Panx1 -/-muscles or muscles treated with Panx1 HC blockers do not show potentiation of the contraction response promoted by repetitive electrical stimulation [22]. In addition, the application of exogenous ATP to Panx1 -/-muscles promotes potentiation of the contraction response [46]. Another important function of Panx1 HCs is that they are permeable to glucose and account for about 50 % of glucose uptake induced by repetitive electrical stimulation, while the other 50 % is taken over by glucose transporter type 4 [22].…”

Endogenous purines modulate K+‐evoked ACh secretion at the mouse neuromuscular junction

“…On the other hand, it cannot be ruled out that K + depolarization also provokes secretion of purines from other cells (i.e., muscle cells, Schwann cells), contributing to the concentration of purines in the extracellular space. In this regard, pannexin 1 was recently proposed as a possible pathway for ATP release from skeletal muscle (Arias‐Calderón et al, ; Buvinic et al, ; Cea, Riquelme, Vargas, Urrutia, & Sáez, ; Riquelme et al, ), and among other stimuli, high extracellular K + increases the activity of pannexin 1 channels (D'Hondt et al, ). However, pannexin 1 is localized in the sarcolemma of the T‐tubules (Cea et al, ; Cea, Riquelme, Vargas, Urrutia, & Sáez, ; Jorquera et al, ; Riquelme et al, ) far from the synaptic area.…”

“…Asterisks indicate significance with respect to the results obtained in control saline Schwann cells), contributing to the concentration of purines in the extracellular space. In this regard, pannexin 1 was recently proposed as a possible pathway for ATP release from skeletal muscle (Arias-Calder on et al, 2016; Buvinic et al, 2009;Cea, Riquelme, Vargas, Urrutia, & S aez, 2013;Riquelme et al, 2013), and among other stimuli, high extracellular K 1 increases the activity of pannexin 1 channels (D'Hondt FIG URE 6 Effect of 100 mM inosine and 5 mM MRS-1191 (A 3 adenosine receptor agonist and antagonist, respectively) upon K 1 -evoked ACh secretion. (a) Representative MEPPs recorded from diaphragm muscle fibers incubated in control solution (5 mM K 1 , calibration 1 mV, 2,000 ms) and solutions containing 10 mM K 1 (calibration 1 mV, 1,000 ms), 15 mM K 1 (calibration 1 mV, 500 ms), and 20 mM K 1 (calibration 1 mV, 100 ms), in the absence or presence of inosine.…”

“…Asterisks indicate significance with respect to the results obtained in control saline et al, 2013). However, pannexin 1 is localized in the sarcolemma of the T-tubules (Cea et al, 2012;Cea, Riquelme, Vargas, Urrutia, & S aez, 2014;Jorquera et al, 2013;Riquelme et al, 2013) far from the synaptic area. More investigation is needed to elucidate this point.…”

Purinergic signalling during myogenesis: a role for adenosine and its receptors

“…From in vitro experiments, the release of ATP via pannexin‐1 hemi‐channels in rat muscle cells has been shown both before (myoblasts) and after (myotubes) their fusion (Cea et al . ). Under these conditions, the application of other purine nucleotides, including GTP, to the outside of C2C12 muscle cells or mouse muscle stem cells (i.e.…”