Myo-inositol is important for neuromuscular functions

Abstract

Sodium/myo-inositol co-transporter (SMIT) is a membrane protein responsiblefor importing myo-inositol (MI) into the cell. MI is a precursor ofphosphatidylinositol, and also serves as an osmolyte to maintain propercellular osmolarity. To understand the function of SMIT, we generated SMITknockout mice. Homozygous SMIT knockout mice died soon after birth butmaternal MI feeding prevented the lethality, suggesting that there may be otherless efficient transporters to facilitate the cellular uptake of MI. Adult SMITknockout mice that did not receive MI supplement after weaning, had 1/10 thesciatic nerve MI level compared with the wildtype and showed a dramaticreduction in their motor nerve conduction velocity (MNCV). SMIT knockoutmice that received continuous MI supplement showed a small but significantincrease in their sciatic nerve MI content and improved MNCV. Skeletal muscleMI level was also decreased in SMIT knockout mice and continuous MI feedingbrought MI content back to normal. Gastrocnemius mass was reduced in SMITknockout mice and was increased by continuous MI feeding. Functionally,homozygous SMIT knockout mice not receiving MI supplement after weaningshowed a reduction in the length of time that they could hang onto the wire,indicating neuromuscular problem. Depletion of nerve MI may impairphosphatidylinositols synthesis and turnover, and eventually impair proteinkinase C (PKC) and Na+/K+ATPase activity leading to neuropathy. There was asignificant decrease in sciatic nerve PKC activity in SMIT knockout micesuggesting MI depletion in sciatic nerve impaired PKC signaling cascadecausing peripheral neuropathy. The present data suggest that MI is important inmaintaining normal neuromuscular function.