Effects of veratrine on skeletal muscle mitochondria: Ultrastructural, cytochemical, and morphometrical studies

The alkaloid veratrine is a lipid-soluble neurotoxin, which target voltage-gated Na þ channels for their primary action. Recently, we showed that this alkaloid may cause myonec- rosis and evidences suggest mitochondria as one of its cell targets. Herein, we investigate the effects caused by variable concentration of veratrine (250 and 550 lg/mL) on mitochondrial oxygen consumption, respiratory chain enzymes activities, and ultrastructure, combining electron micros- copy with cytochemical and biochemical approaches. The results showed different sort of ultra- structural changes, both in isolated and intramuscular mitochondria. Veratrine decreased mito- chondrial nicotinamide adenine dinucleotide dehydrogenase (NADH-d), succinic dehydrogenase (SDH), and cytochrome oxidase (COX) activities, significantly and dose-dependently inhibited the state 3 respiration rate, respiratory control ratio (RCR), and ADP/O on isolated rat skeletal muscle mitochondria, whereas state 4 was unaffected. A tendency of increase in mitochondria diameter was seen with 250 lg/mL veratrine. We conclude that the alkaloid would probably act on mitochon- drial membrane phospholipid configuration, which would explain the changes observed. Microsc. Res. Tech. 69:108-118, 2006. V C 2006 Wiley-Liss, Inc.