No evidence for inositol 1,4,5-trisphosphate–dependent Ca2+ release in isolated fibers of adult mouse skeletal muscle

Abstract

The presence and role of functional inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) in adult skeletal muscle are controversial. The current consensus is that, in adult striated muscle, the relative amount of IP3Rs is too low and the kinetics of Ca2+ release from IP3R is too slow compared with ryanodine receptors to contribute to the Ca2+ transient during excitation–contraction coupling. However, it has been suggested that IP3-dependent Ca2+ release may be involved in signaling cascades leading to regulation of muscle gene expression. We have reinvestigated IP3-dependent Ca2+ release in isolated flexor digitorum brevis (FDB) muscle fibers from adult mice. Although Ca2+ transients were readily induced in cultured C2C12 muscle cells by (a) UTP stimulation, (b) direct injection of IP3, or (c) photolysis of membrane-permeant caged IP3, no statistically significant change in calcium signal was detected in adult FDB fibers. We conclude that the IP3–IP3R system does not appear to affect global calcium levels in adult mouse skeletal muscle.

Cav1.1 controls frequency-dependent events regulating adult skeletal muscle plasticity

“…In electrically stimulated adult muscle fibers, Ins(1,4,5)P 3 -evoked Ca 2+ signals mediate the frequency-dependent activation of slow-phenotype muscle fiber genes (TnIs) and repression of fastphenotype fibers genes (TnIf) (Casas et al, 2010). In a recent publication (Blaauw et al, 2012), lack of calcium signals in response to Ins(1,4,5)P 3 uncaging in adult muscle fibers was reported; there are several reasons why such signals may be hard to record, including some dependence of Ins(1,4,5)P 3 -induced Ca 2+ release on membrane potential and/or intracellular Ca 2+ concentration (Rojas and Jaimovich, 1990) or even mitochondria dumping of the calcium transient (Eisner et al, 2010). The fact that such transients can be evidenced after tetanic stimulation (Casas et al, 2010) and that Ins(1,4,5)P 3 R inhibition blocks expression of particular genes, suggests that the precise location, magnitude and regulation of this signaling system should be a matter of further studies.…”

Angiotensin II modulates mouse skeletal muscle resting conductance to chloride and potassium ions and calcium homeostasis via the AT1 receptor and NADPH oxidase

“…As a classical paradigm, such a transduction signal produces diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (IP 3 ). While recent evidence demonstrated that IP 3 plays a marginal, if any, role in releasing Ca 2ϩ from muscle SR stores (3), DAG can directly activate PKC and also reinforce the signaling by stimulating receptor-mediated calcium entry via activation of transient receptor potential (TRP) channels, such as TRPC5 and 6 (1,38).…”

Type 1 Inositol (1,4,5)-Trisphosphate Receptor Activates Ryanodine Receptor 1 to Mediate Calcium Spark Signaling in Adult Mammalian Skeletal Muscle

“…Many subsequent studies from other investigators have revealed a role for IP 3 R in facilitating the RyR-mediated Ca 2ϩ release in smooth muscle and cardiac muscle. Recent studies from Jaimovich and colleagues (18) demonstrated a role for IP 3 R in modulation of excitation-transcription coupling in skeletal muscle; however, controversy exists in this topic as Blaauw et al (24) did not find a significant role for IP 3 in skeletal muscle Ca 2ϩ signaling. The observation that uncaging of IP 3 alone could not produce Ca 2ϩ spark events in muscle fibers without pre-exposure to osmotic stress suggests the possibility that other factors such as physical uncoupling of voltage sensor from RyR during osmotic stress could be required for induction of the robust Ca 2ϩ spark events (4,25).…”