Effect of protein kinase Cbeta inhibitor on Ca2+ homeostasis in diabetic sensory neurons.
To elucidate the direct effect of selective protein kinase Cbeta inhibitor LY333531 on diabetic sensory neurons, we examined intracellular Ca(2+) concentration in isolated rat dorsal root ganglion neurons using the fluorescent Ca(2+) indicator fura-2. The duration of calcium transients induced by high (50 mM) extracellular K in small diabetic dorsal root ganglion neurons was significantly prolonged compared with that in control neurons. This prolonged intracellular Ca concentration elevation in diabetic neurons was normalized rapidly and reversibly by LY333531 in a dose-dependent manner, and the effect of LY333531 was completely abolished by pretreating the neurons with mitochondrial calcium uniporter inhibitor, Ruthenium 360. These results suggest that LY333531 has an ameliorating effect on calcium homeostasis of diabetic sensory neurons via mitochondrial calcium buffering.
Tahara
Masayuki
M
Division of Neurology, Department of Internal Medicine, Shiga University of Medical Science, Otsu, Shiga, Japan.
Omatsu-Kanbe
Mariko
M
Sanada
Mitsuru
M
Maeda
Kengo
K
Koya
Daisuke
D
Matsuura
Hiroshi
H
Kashiwagi
Atsunori
A
Yasuda
Hitoshi
H
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005727:Ganglia, Spinal / Q000473:pathology; D006706:Homeostasis / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D009475:Neurons, Afferent / Q000187:drug effects* / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; D011189:Potassium Chloride; C099154:ruboxistaurin; D011493:Protein Kinase C; D002118:Calcium