TY - JOUR
T1 - Role of protein kinase C in insulin activation of the Na-K pump in cultured skeletal muscle
AU - Sampson, S. R.
AU - Brodie, C.
AU - Alboim, S. V.
PY - 1994/3
Y1 - 1994/3
N2 - Administration of insulin to preparations of skeletal muscle causes an increase in Na+-K+ pump activity within 15-30 min. Although several mechanisms have been proposed, such as promotion of Na+ influx and translocation of pumps from intracellular to membrane sites, the early events involved in this effect remain unknown. We have investigated the possibility that activation of protein kinase C (PKC) may be an initial event in Na+- K+ pump activation in primary cultures of rat skeletal muscle. Insulin (80- 100 mU/ml) and tumor-promoting phorbol esters (10-100 nM) increased Na+-K+ pump activity as determined by measurements of ouabain-suppressible 86Rb uptake, electrogenic pump component of membrane potential, and specific [3H]ouabain binding. These effects were not reduced by treatment of myotubes with amiloride, which blocks Na+-H+ exchange, or with tetrodotoxin, which blocks voltage-dependent Na+ channels. Effects of insulin and phorbol esters were not additive, suggestive of a common mechanism. Effects of both phorbol esters and insulin were significantly reduced by staurosporine (50-100 nM) and by downregulation of PKC (by pretreatment of myotubes with phorbol ester for 24 h). The findings suggest that insulin may stimulate Na+-K+ pump activity in skeletal muscle by activation of PKC.
AB - Administration of insulin to preparations of skeletal muscle causes an increase in Na+-K+ pump activity within 15-30 min. Although several mechanisms have been proposed, such as promotion of Na+ influx and translocation of pumps from intracellular to membrane sites, the early events involved in this effect remain unknown. We have investigated the possibility that activation of protein kinase C (PKC) may be an initial event in Na+- K+ pump activation in primary cultures of rat skeletal muscle. Insulin (80- 100 mU/ml) and tumor-promoting phorbol esters (10-100 nM) increased Na+-K+ pump activity as determined by measurements of ouabain-suppressible 86Rb uptake, electrogenic pump component of membrane potential, and specific [3H]ouabain binding. These effects were not reduced by treatment of myotubes with amiloride, which blocks Na+-H+ exchange, or with tetrodotoxin, which blocks voltage-dependent Na+ channels. Effects of insulin and phorbol esters were not additive, suggestive of a common mechanism. Effects of both phorbol esters and insulin were significantly reduced by staurosporine (50-100 nM) and by downregulation of PKC (by pretreatment of myotubes with phorbol ester for 24 h). The findings suggest that insulin may stimulate Na+-K+ pump activity in skeletal muscle by activation of PKC.
KW - amiloride
KW - membrane potential
KW - ouabain
KW - phorbol esters
UR - http://www.scopus.com/inward/record.url?scp=0028084172&partnerID=8YFLogxK
U2 - 10.1152/ajpcell.1994.266.3.c751
DO - 10.1152/ajpcell.1994.266.3.c751
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C2 - 8166238
AN - SCOPUS:0028084172
SN - 0002-9513
VL - 266
SP - C751-C758
JO - American Journal of Physiology - Cell Physiology
JF - American Journal of Physiology - Cell Physiology
IS - 3 35-3
ER -