Kv1.3 inhibitors have differential effects on glucose uptake and AMPK activity in skeletal muscle cell lines and mouse ex vivo skeletal muscle

TY - JOUR

T1 - Kv1.3 inhibitors have differential effects on glucose uptake and AMPK activity in skeletal muscle cell lines and mouse ex vivo skeletal muscle

AU - Hamilton, D Lee

AU - Beall, Craig

AU - Jeromson, Stewart

AU - Chevtzoff, Cyrille

AU - Cuthbertson, Daniel J

AU - Ashford, Michael L J

PY - 2014/1

Y1 - 2014/1

N2 - Knockout of Kv1.3 improves glucose homeostasis and confers resistance to obesity. Additionally, Kv1.3 inhibition enhances glucose uptake. This is thought to occur through calcium release. Kv1.3 inhibition in T-lymphocytes alters mitochondrial membrane potential, and, as many agents that induce Ca(2+) release or inhibit mitochondrial function activate AMPK, we hypothesised that Kv1.3 inhibition would activate AMPK and increase glucose uptake. We screened cultured muscle with a range of Kv1.3 inhibitors for their ability to alter glucose uptake. Only Psora4 increased glucose uptake in C2C12 myotubes. None of the inhibitors had any impact on L6 myotubes. Magratoxin activated AMPK in C2C12 myotubes and only Pap1 activated AMPK in the SOL. Kv1.3 inhibitors did not alter cellular respiration, indicating a lack of effect on mitochondrial function. In conclusion, AMPK does not mediate the effects of Kv1.3 inhibitors and they display differential effects in different skeletal muscle cell lines without impairing mitochondrial function.

AB - Knockout of Kv1.3 improves glucose homeostasis and confers resistance to obesity. Additionally, Kv1.3 inhibition enhances glucose uptake. This is thought to occur through calcium release. Kv1.3 inhibition in T-lymphocytes alters mitochondrial membrane potential, and, as many agents that induce Ca(2+) release or inhibit mitochondrial function activate AMPK, we hypothesised that Kv1.3 inhibition would activate AMPK and increase glucose uptake. We screened cultured muscle with a range of Kv1.3 inhibitors for their ability to alter glucose uptake. Only Psora4 increased glucose uptake in C2C12 myotubes. None of the inhibitors had any impact on L6 myotubes. Magratoxin activated AMPK in C2C12 myotubes and only Pap1 activated AMPK in the SOL. Kv1.3 inhibitors did not alter cellular respiration, indicating a lack of effect on mitochondrial function. In conclusion, AMPK does not mediate the effects of Kv1.3 inhibitors and they display differential effects in different skeletal muscle cell lines without impairing mitochondrial function.

KW - Ampk

KW - Glucose uptake

KW - Kv1.3

KW - Skeletal muscle

UR - https://www.scopus.com/pages/publications/84895830891

U2 - 10.1007/s12576-013-0285-4

DO - 10.1007/s12576-013-0285-4

M3 - Article

C2 - 24043354

SN - 1880-6546

VL - 64

SP - 13

EP - 20

JO - Journal of Physiological Sciences

JF - Journal of Physiological Sciences

IS - 1

ER -