Regulation of muscle AChR α subunit gene expression by electrical activity: Involvement of protein kinase C and Ca 2+

Protein Kinase C and Calcium/Calmodulin-activated Protein Kinase II (CaMK II) Suppress Nicotinic Acetylcholine Receptor Gene Expression in Mammalian Muscle

“…In contrast, when denervated muscle is electrically stimulated, intracellular calcium concentrations are elevated (4), and receptor expression is suppressed (6 -8). Similarly, receptor expression is suppressed in TTX-treated myotubes when they are exposed to calcium-elevating drugs (2,3,9,10). Although muscle depolarization and increases in intracellular calcium can initiate the process of nAChR suppression in extrajunctional nuclei, the signal transduction pathways involved in these processes remain controversial.…”

“…Experiments performed in avian muscle have implicated protein kinase C (PKC) as the primary mediator of activity-dependent, calcium-induced suppression of nAChR gene expression (2,7,11). The proposed model of suppression involves depolarization-dependent activation of a calcium-and phospholipid-dependent PKC (4,12).…”

“…Depolarization-dependent suppression of nAChR gene expression has been attributed to increases in intracellular calcium (2,3). When skeletal muscle is made inactive by denervation or pharmacological treatment with drugs such as the sodium channel blocker tetrodotoxin (TTX), calcium concentrations remain low (4), and extrajunctional expression of the nAChR genes is increased dramatically (5,6).…”

“…Although there is ample evidence that PKC participates in mediating the effects of muscle activity on nAChR gene expression in birds (2,7,11), there is little evidence supporting this regulatory mechanism in mammalian muscle (10). Moreover, although previous experiments have suggested that a phorbol ester-responsive PKC mediates nAChR gene expression by muscle depolarization in chick muscle, recent experiments have not supported these data and suggest that an atypical PKC may be involved (11).…”

Different mechanisms of Ca2+‐handling following nicotinic acetylcholine receptor stimulation, P2U‐purinoceptor stimulation and K+‐induced depolarization in C2C12 myotubes

“…A short-term increase in & Hodges-Savola, 1992). cellular Ca2`enhances the rate of desensitization of nicotine Stimulation of myotubes with the transmitter of motor acetylcholine receptors (nAChRs; Miledi, 1980), while a longneurones (acetylcholine), its co-transmitter ATP (Silinsky, term increase in Ca2" is involved in down-regulation of 1975) and depolarization of the myotubes have all been renAChRs (Smilowitz et al, 1988;Klarsfeld et al, 1989; ported to increase intracellular Ca2" in myotubes. In myotubes of different origin, the ACh-sensitive receptor which is involved in augmenting Ca2" has invariably been characterized ____________________ as the muscle type nicotinic receptor (Giovannelli et al, 1991; ceptors (P2-purinoceptors) is still largely based on their sensitivity to ATP analogues (Cusack & Hourani, 1990), because of the lack of a specific antagonist at cloned receptors (Webb et al, 1993;Lustig et al, 1993).…”