Myosin Va is developmentally regulated and expressed in the human cerebellum from birth to old age

Myosin Va functions as a processive, actin-based motor molecule highly enriched in the nervous system, which transports and/or tethers organelles, vesicles, and mRNA and protein translation machinery. Mutation of myosin Va leads to Griscelli disease that is associated with severe neurological deficits and a short life span. Despite playing a critical role in development, the expression of myosin Va in the central nervous system throughout the human life span has not been reported. To address this issue, the cerebellar expression of myosin Va from newborns to elderly humans was studied by immunohistochemistry using an affinity-purified anti-myosin Va antibody. Myosin Va was expressed at all ages from the 10th postnatal day to the 98th year of life, in molecular, Purkinje and granular cerebellar layers. Cerebellar myosin Va expression did not differ essentially in localization or intensity from childhood to old age, except during the postnatal developmental period. Structures resembling granules and climbing fibers in Purkinje cells were deeply stained. In dentate neurons, long processes were deeply stained by anti-myosin Va, as were punctate nuclear structures. During the first postnatal year, myosin Va was differentially expressed in the external granular layer (EGL). In the EGL, proliferating prospective granule cells were not stained by anti-myosin Va antibody. In contrast, premigratory granule cells in the EGL stained moderately. Granule cells exhibiting a migratory profile in the molecular layer were also moderately stained. In conclusion, neuronal myosin Va is developmentally regulated, and appears to be required for cerebellar function from early postnatal life to senescence.

Participation of ATP-sensitive K+ channels in the peripheral antinociceptive effect of fentanyl in rats

We examined the effect of several K+ channel blockers such as glibenclamide, tolbutamide, charybdotoxin (ChTX), apamin, tetraethylammonium chloride (TEA), 4-aminopyridine (4-AP), and cesium on the ability of fentanyl, a clinically used selective æ-opioid receptor agonist, to promote peripheral antinociception. Antinociception was measured by the paw pressure test in male Wistar rats weighing 180-250 g (N = 5 animals per group). Carrageenan (250 æg/paw) decreased the threshold of responsiveness to noxious pressure (delta = 188.1 ± 5.3 g). This mechanical hyperalgesia was reduced by fentanyl (0.5, 1.5 and 3 æg/paw) in a peripherally mediated and dose-dependent fashion (17.3, 45.3 and 62.6 percent, respectively). The selective blockers of ATP-sensitive K+ channels glibenclamide (40, 80 and 160 æg/paw) and tolbutamide (80, 160 and 240 æg/paw) dose dependently antagonized the antinociception induced by fentanyl (1.5 æg/paw). In contrast, the effect of fentanyl was unaffected by the large conductance Ca2+-activated K+ channel blocker ChTX (2 æg/paw), the small conductance Ca2+-activated K+ channel blocker apamin (10 æg/paw), or the non-specific K+ channel blocker TEA (150 æg/paw), 4-AP (50 æg/paw), and cesium (250 æg/paw). These results extend previously reported data on the peripheral analgesic effect of morphine and fentanyl, suggesting for the first time that the peripheral æ-opioid receptor-mediated antinociceptive effect of fentanyl depends on activation of ATP-sensitive, but not other, K+ channels.