IP3-dependent, post-tetanic calcium transients induced by electrostimulation of adult skeletal muscle fibers

Abstract

Tetanic electrical stimulation induces two separate calcium signals in rat skeletal myotubes, a fast one, dependent on Cav 1.1 or dihydropyridine receptors (DHPRs) and ryanodine receptors and related to contraction, and a slow signal, dependent on DHPR and inositol trisphosphate receptors (IP3Rs) and related to transcriptional events. We searched for slow calcium signals in adult muscle fibers using isolated adult flexor digitorum brevis fibers from 5–7-wk-old mice, loaded with fluo-3. When stimulated with trains of 0.3-ms pulses at various frequencies, cells responded with a fast calcium signal associated with muscle contraction, followed by a slower signal similar to one previously described in cultured myotubes. Nifedipine inhibited the slow signal more effectively than the fast one, suggesting a role for DHPR in its onset. The IP3R inhibitors Xestospongin B or C (5 µM) also inhibited it. The amplitude of post-tetanic calcium transients depends on both tetanus frequency and duration, having a maximum at 10–20 Hz. At this stimulation frequency, an increase of the slow isoform of troponin I mRNA was detected, while the fast isoform of this gene was inhibited. All three IP3R isoforms were present in adult muscle. IP3R-1 was differentially expressed in different types of muscle fibers, being higher in a subset of fast-type fibers. Interestingly, isolated fibers from the slow soleus muscle did not reveal the slow calcium signal induced by electrical stimulus. These results support the idea that IP3R-dependent slow calcium signals may be characteristic of distinct types of muscle fibers and may participate in the activation of specific transcriptional programs of slow and fast phenotype.

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

“…At this stimulation frequency, an increase of TnIs and a decrease in TnIf mRNA levels take place (Casas et al, 2010), a characteristic feature of fast-to-slow fiber phenotype transition.…”

Altered Gene Expression Pathways in Duchenne Muscular Dystrophy

“…In normal adult mice skeletal muscle, we observed that IP 3 R immuno-labeling follows distinctive patters resembling the SR (types 1, 2 and 3 IP 3 Rs), sarcolemmal (types 1 and 3 IP 3 Rs) or nuclear localizations (types 1 and 3 IP 3 Rs) (Casas et al 2010). The labeling for both type 1 and type 2 IP 3 Rs subtypes showed a fiber type-specific distribution with much higher expression in fast (type II) muscle fibers, whereas type 3 IP 3 R showed a uniform distribution in both fiber types, as shown by co-labeling with slow myosin heavy chain antibody.…”

“…IP 3 mediated Ca 2+ signals induce both a transient activation of ERK½ and transcription factor CREB, and an increase in early genes (c-fos, c-jun and egr-1) and in late genes (troponin I, interleukin-6, hmox and hsp70) mRNA levels after depolarization of normal skeletal muscle cells Juretic et al 2006;Juretic et al 2007;Jorquera et al 2009). Moreover, in electrically stimulated adult muscle fibers, slow Ca 2+ signals mediate the frequency-dependent activation of slowphenotype muscle fiber genes (slow troponin I, TnIs) and repression of fast-phenotype ones (TnIf) (Casas et al 2010). These evidences link slow Ca 2+ transients with muscular effects of nerve activity and with the process of muscle cell plasticity.…”

“…The labeling for both type 1 and type 2 IP 3 Rs subtypes showed a fiber type-specific distribution with much higher expression in fast (type II) muscle fibers, whereas type 3 IP 3 R showed a uniform distribution in both fiber types, as shown by co-labeling with slow myosin heavy chain antibody. Likewise, mice muscle fibers show a characteristic mosaic pattern for type 1 IP 3 R (Casas et al 2010). When human muscle was studied, type II muscle fibers showed a much more intense labeling for the IP 3 R subtype 1 compared to type I (slow) fibers.…”

Depression of voltage-activated Ca2+release in skeletal muscle by activation of a voltage-sensing phosphatase

“…It should be mentioned though that this does not exclude the potential for Ins(1,4,5)P 3 to be involved in Ca 2+ signals with a physiological purpose other than contraction, either in a voltage-dependent (Casas et al, 2010;Jorquera et al, 2013) or voltage-independent manner (Tjondrokoesoemo et al, 2013). On the other hand, considering the growing number of proteins and specifically of voltage-dependent and voltage-independent ion channels that are sensitive to the PtdIns(4,5)P 2 level in the plasma membrane, it was of strong interest to investigate whether the function of the E-C coupling molecular machinery would be dependent on PtdIns(4,5)P 2 level.…”