Lipid droplet accumulation in cardiac muscle cells of the bat: Potential auto‐toxicity of the cardiac sympathetic innervation

Abstract

The previously described ability of reserpine and parachlorophenylalanine to induce the accumulation of lipid droplets in ventricular cardiac muscle cells of the bat was investigated. Lipid droplet accumulation was assessed qualitatively by light microscopy and quantitatively by morphometric analysis of electron micrographs. An hypothesis that the action of the drugs was an indirect one, mediated by the cardiac adrenergic innervation, was framed and tested. Lipid droplet accumulation occurred during a time of intense sympathetic activity, that of arousal from hibernation. The ability of the two drugs to produce the effect was antagonized by prior sympathectomy with 6-hydroxy-dopamine.The effect was mimicked by administration of exogenous norepinephrine together with inhibitors of its catabolic enzymes, monoamine oxidase and catechol-omethyl transferase. These observations are all consistent with the initial hypothesis and raise the possibility that endogenous norepinephrine in the cardiac sympathetic innervation might be, at least potentially, auto-toxic.The accumulation ad lipid droplets in cardiac muscle cells of the bat's cardiac ventricle has been observed in animals treated with the drug reserpine (Hagopian et al., '72). Similar chainges have also been induced in the hearts of active bats by the administration of parachlorophenylalanine (PCPA: Hagopian et al., '73a). Reserpine depIetes tissues of both serotonin and catecholamines (Carlsson, '66, for references) while PCPA, a tryptophan hydroxylase inhibitor, essentially depletes only serotonin (Koe and Weissman, ' 168). In subsequent experiments bats were given 6-hydroxydopamine (6-HD: Hagopian et al., '73b), a drug known to cause depletion of norepinephrine (NE) from tissues by effecting a chemical sympathectomy (Malmfors and Thoenen, '71). 6-HD did deplete the bat's heart of NE and evidence of degeneration of adrenergic axon terminals was obtained. However, no lipid accumulation in cardiac muscle cells was associated with these effects of the drug (Hagopian et al., '73b droplets to accumulate in cardiac muscle cells and, in the previous instance (after PCPA) lipid droplets could be induced to accumulate without an accompanying depletion of catecholamines. Therefore, it seems clear that depletion of catecholamines is not causally related to lipid droplet accumulation in cardiocytes. The action of PCPA and reserpine must be explained in other terms. The effect of PCPA is particularly interesting since the heart contains very little serotonin (Snyder et al., '65). This raises the possibility that lipid droplet accumulation may be an indirect effect of the drugs, resulting from their action on the central nervous system and mediated through the cardiac innervation.The catecholamines, isoproterenol and NE, have been reported to induce a cardiomyopathy associated with lipid accumulation in cardiac muscle cells (Ferrans et al., '64; Regan et al., '72). These observations suggest that adrenergic nerves may provide the common pathway used by the drugs to...

Ultrastructure of the Ventricular Myocardium of the Bat <i>Eidolon helvum</i>

“…1979: Hagopian and Nunez. 1972: Kawamura and James, 1971Kawamura et al" 1978: Nunez et al" 1975. However, in our studies on the West African straw-coloured (fruit-eating) bat Eidolon helvum, we have observed that the T-tubules in myocardial cells are subs tantially wider than in species such as the rat and that cyto plasmic organelles such as lipid droplets and mitochondria are much more numerous.…”

Ultrastructure of the atrioventricular node of the big brown bat, <i>Eptesicus fucus</i>

“…Nunez et al [1975] suggested that these d roplets acc u m u la te i n t he myocard i u ni d uring times of intense sympathetic activity such as arousal from hibernation. Other cellular com ponents encountered in the nodal cells were Golgi apparatus, vacuoles, smooth and rough endoplasmic reticulum, glycogen deposits and subsarcolemmal vesicles.…”

miR-130b inhibits proliferation and promotes differentiation in myocytes via targeting Sp1

“…When muscle damage or myopathy occurs, the satellite cells are activated and become myoblasts, then proliferate and differentiate into myotubes, and then form myofibers ( He et al, 2004 ). Most muscle disorders are accompanied by abnormal myoblast proliferation and myogenic differentiation ( Nunez et al, 1975 ). In addition, growing evidence has indicated that miRNA functions as a key regulator during myoblast proliferation and myogenic differentiation ( Altshuler-Keylin et al, 2016 ; Lu et al, 2018 ).…”