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    Interplay Between Cholinergic and Adenosinergic Systems in Skeletal Muscle

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    Since the pioneering works of Ricardo Miledi, the neuromuscular junction represents the best example of a synapse where ACh is the neurotransmitter acting on nicotinic ACh receptors. ATP, co-released with ACh, is promptly degraded to Ado, which acts as a modulator of the cholinergic synaptic activity. Consequently, both ACh and adenosine play a crucial role in controlling the nerve-muscle communication. Apart from their role in the context of synaptic transmission, ACh and adenosine are autocrinally released by skeletal muscle cells, suggesting also a non nerve-driven function of these molecules. Indeed, the existence of cholinergic and adenosinergic systems has been widely described in many other non neuronal cell types. In this review, we will describe the two systems and their interplay in non-innervated differentiating skeletal muscle cells, and in innervated adult skeletal muscle fibers. We believe that the better comprehension of the interactions between the activity of nAChRs and adenosine could help the knowledge of skeletal muscle physiology

    Effects of H2O2 on electrical membrane properties of skeletal myotubes

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    Reactive oxygen species (ROS), normally generated in skeletal muscles, could control excitability of muscle fibers through redox modulation of membrane ion channels. However, the mechanisms of ROS action remain largely unknown. To investigate the action of ROS on electrical properties of muscle cells, patch-clamp recordings were performed after application of hydrogen peroxide (H2O2) to skeletal myotubes. H2O2 facilitated sodium spikes after a hyperpolarizing current pulse, by decreasing the latency for spike initiation. Importantly, the antioxidant N-acetylcysteine induced the opposite effect, suggesting the redox control of muscle excitability. The effect of H2O2 was abolished in the presence of catalase. The kinetics of sodium channels were not affected by H2O2. However, the fast inward rectifier K+ (KIR) currents, activated by hyperpolarization, were reduced by H2O2, similar to the action of the potassium channel blockers Ba2+ and Cs+. The block of the outward tail current contributing to KIR deactivation can explain the shorter latency for spike initiation. We propose that the KIR current is an important target for ROS action in myotubes. Our data would thus suggest that ROS are involved in the control of the excitability of myotubes and, possibly, in the oscillatory behavior critical for the plasticity of developing muscle cells

    Electrophysiological characterization of “giant” cells in stratum radiatum of the CA3 hippocampal region

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    Whole cell patch-clamp recording and intracellular staining with biocytin allowed the morphological and electrophysiological characterization of “giant” cells, studied in stratum (st.) radiatum of the CA3 region in 17- to 21-day-old rat hippocampal slices. These neurons had extensive dendritic arborization, a triangular soma, and a bipolar vertical orientation with axons directed to the pyramidal layer or extended into the st. oriens. Giant cells had significantly higher input resistance and shorter action potentials compared with CA3 pyramidal cells. Evoked action potentials were typically followed by an afterdepolarizing potential (ADP). During depolarizing current injection, most (80%) of recorded giant cells displayed a regular firing pattern (maximum steady-state firing rate, ∼30 Hz) characterized by a modest early accommodation, whereas irregular firing was observed in the remaining 20% of giant cells. Hyperpolarizing current pulses induced a slow inward rectification of the electrotonic voltage responses, blocked by 2 mM external Cs+. N-methyl-d-aspartate (NMDA) and non-NMDA–mediated excitatory postsynaptic currents (EPSCs) measured under voltage clamp were distinguished on the basis of their voltage dependence and sensitivity to specific NMDA and non-NMDA glutamate receptor blockers. Non-NMDA EPSCs possessed a linear current-voltage relationship. EPSCs elicited by st. lucidum stimulation were reversibly reduced (mean, 23%) by the group II metabotropic glutamate receptor agonist (2S, 1′R, 2′R, 3′R)-2-(2,3-dicarboxyl-cyclopropyl)-glycine (DCG-IV, 1 μM). GABAA-mediated postsynaptic currents were subject to paired-pulse depression that was inhibited by the GABAB antagonist CGP 55845A (5 μM). We conclude that CA3 giant cells represent a particular class of hippocampal neuron located in st. radiatum that shares only some morphological and physiological properties with principal cells. </jats:p
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