A Novel Hypothesis About Mechanisms Affecting Conduction Velocity of Central Myelinated Fibers

Abstract

The hypothesis that gap junctions are implicated in facilitating axonal conduction has not yet been experimentally demonstrated at the electrophysiological level. We found that block of gap junctions with oleammide slows down axonal conduction velocity in the hippocampal Schaffer collaterals, a central myelinated pathway. Moreover, we explored the possibility that support by the oligodendrocyte to the axon involves energy metabolism, a hypothesis that has been recently proposed by some of us. In agreement with this hypothesis, we found that the effect of oleammide was reversed by pretreatment with creatine, a compound that is known to increase the energy charge of the tissue. Moreover, conduction velocity was also slowed down by anoxia, a treatment that obviously decreases the energy charge of the tissue, and by ouabain, a compound that blocks plasma membrane Na/K-ATPase, the main user of ATP in the brain. We hypothesize that block of gap junctions slows down conduction velocity in central myelinated pathways because oligodendrocytes synthesize ATP and transfer it to the axon through gap junctions.

Age-Related Visual Signal Changes Induced by Hypoxemic Hypoxia

“…Different trials have in fact shown that the oxygen deprivation quickly affects the nerve fibers, either myelinated or unmyelinated, throughout the central nervous system (Adriano et al, 2011;Banasiak and Haddad, 1998). The results obtained regarding this parameter mostly agree with those obtained from previous publications (Singh et al, 2004a;Thakur et al, 2005;Tsarouchas et al, 2008).…”

Extramitochondrial energy production in platelets

“…Data show that in untreated conditions, only 13% of consumed glucose is converted to lactate. This value increased to 60% when platelets were treated with atractyloside, a specific inhibitor of the mitochondrial adenine nucleotide translocator (ANT) and hence of the mitochondrial OXPHOS [Adriano et al., ].…”

Chemiosmotic coupling in oxidative phosphorylation: The history of a hard experimental effort hampered by the Heisenberg indeterminacy principle

“…The Chemiosmotic Theory (Mitchell, 1961) as it was formulated is a process that can only take place in organelle possessing double membrane systems forming closed compartments to entrap protons, such as mitochondrial cristae, bacteria and thylakoids. Here, for the sake of simplicity, we have considered the mitochondrial inner membrane, even though in recent years, it has been shown that the oxidative phosphorylation (OXPHOS), coupled to aerobic ATP synthesis, also occurs in extra-mitochondrial districts, as rod outer segment (OS ) disks (Calzia et al, 2014) (Calzia et al, 2013) (Bianchini et al, 2008) (Panfoli et al, 2009), myelin sheath (Ravera et al, 2009) (Ravera et al, 2011b) (Morelli et al, 2011) (Ravera et al, 2015), plasma membrane (Mangiullo et al, 2008) (Arakaki et al, 2003) (Arakaki et al, 2007 (Adriano et al, 2011) (Chang et al, 2012) (Lee et al, 2016) (Taurino & Gnoni, 2018) (Taurino et al, 2016) (Gao et al, 2017) extracellular vesicles shedding form cells, such as exosomes and microvesicles, which seem to carry an unsuspected metabolic signature (Panfoli et al, 2016). In particular, recent data indicate an active extramitochondrial OXPHOS in the endoplasmic reticulum of platelets which both have elevated ATP need but possess very little mitochondria (Ravera et al, 2018).…”

“…In fact, it was demonstrated that many biological membranes, devoid of closed compartments and of mitochondria, conduct OXPHOS with high efficiency (Calzia et al, 2010) (Roehlecke et al, 2013) (Mangiullo et al, 2008) (Panfoli et al, 2012) (Ravera et al, 2011b) (Ravera et al, 2013) (Ravera et al, 2018) , challenging the idea that it is exclusive of mitochondria, thylakoid and bacteria. Of particular interest are the reports of the ability of plasma membranes to synthesize ATP outside the cell, as they harbour the five complexes of respiration (Mangiullo et al, 2008) (Arakaki et al, 2003) (Arakaki et al, 2007) (Adriano et al, 2011) (Chang et al, 2012) (Lee et al, 2016).…”