Naslov
Regulation of Na, K pump and Na+ & K+ channels in diabetic neuropathy

Autori
Maysinger, D ; Križ, J ; Hashiguchi, T ; Pađen, A.L.

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Society for Neuroscience : Abstracts / Society for Neuroscience - Washington (MD) : Society for Neuroscience, 1997, 830-830

Skup
27th Annual Meeting, Society for Neuroscience

Mjesto i datum
New Orleans (LA), Sjedinjene Američke Države, 25.10.1997. - 30.10.1997

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
diabetic neuropathy; NaK pump; ion channels

Sažetak
Diabetic neuropathy (DN) is associated with a decrease in conduction velocity of peripheral nerves presumably as a result of metabolic dysfunction that affects Na, K-ATPase (NKA) activity and Na+ channels (NC). In order to characterize the functional defect(s) in DN we have used peripheral nerves of streptozotocin-induced diabetic rats (STZ) rats. For studies of regulation of NKA and NC by growth factors (NGF, EGF) we have used PC12 model system. Findings: 1) The rate constant of decay of post-tetanic hyperpolarization (PTH; trains of 50-120 s, 50-300 Hz), an electrophysiological correlate of Na, K-pumping (as evidence by its blockade by 2,4-dinitrophenol, Na-azide, ouabain, low [K+]o and by [Li+]o replacement of [Na+]o), was significantly decreased in peripheral nerves from STZ rats (from 4.38ą1.2 x 10-3 /s,n=30; 3 months post STZ injection); the area of PTH was also decreased. These results correlated well with decreased activity on NKA in the same nerves. The slope of frequency of stimulation vs. area of PTH was decreased in diabetic rats suggesting a more pronounced defect in pumping a higher frequencies. Intra-axonal microelectrode recordings from large myelinated axons in STZ rats showed decreased resting memb! rane potential and possibly a decrease in inward rectification. 2) Chronic exposure of PC12 to NGF (5 d, 20 ng/ml) induced expression of catalytic a1 subunit Na,K-ATPase, in addition to Na+ channels. Exposure to EGF (5-15 min; 100 ng/ml) caused notiveable decrease in serine - threonine phosphorylation of Na,K-ATPase . Neither EGF (5 ng/mL) nor insulinomimetic peroxovanadate (100 nbM) alone affecte NKA but when combined, they led to a significant increase in enzymatic activity. Studies of Na,K pumping on PC12 are in progress. Conclusion: These results demonstrate a functional defect in NaK pumping in DN and alterations in membrane conductances of peripheral nerves in DN. This model system may be useful for further studies of DN mechanisms and for therapeutic interventions

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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