Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by... more Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by chorea, incoordination and psychiatric and behavioral symptoms. The leading cause of death in HD patients is aspiration pneumonia, associated with respiratory dysfunction, decreased respiratory muscle strength and dysphagia. Although most of the motor symptoms are derived from alterations in the central nervous system, some might be associated with changes in the components of motor units (MU). To explore this hypothesis, we evaluated morphofunctional aspects of the diaphragm muscle in a mouse model for HD (BACHD). We showed that the axons of the phrenic nerves were not affected in 12-months-old BACHD mice, but the axon terminals that form the neuromuscular junctions (NMJs) were more fragmented in these animals in comparison with the wild-type mice. In BACHD mice, the synaptic vesicles of the diaphragm NMJs presented a decreased exocytosis rate. Quantal content and quantal size were sma...
Substance P modulates ion channels and the excitability of sensory neurons in pain pathways. With... more Substance P modulates ion channels and the excitability of sensory neurons in pain pathways. Within the heterogeneous population of Dorsal Root Ganglia (DRG) primary sensory neurons, the properties of cells that are sensitive to Substance P are poorly characterized. To define this population better, dissociated rat DRG neurons were tested for their responsiveness to capsaicin, ATP and acid. Responses to ATP were classified according to the kinetics of current activation and desensitization. The same cells were then tested for modulation of action potential firing by Substance P. Acid and capsaicin currents were more frequently encountered in the largest diameter neurons. P2X3-like ATP currents were concentrated in small diameter neurons. Substance P modulated the excitability in 20 of 72 cells tested (28%). Of the Substance P sensitive cells, 10 exhibited an increase in excitability and 10 exhibited a decrease in excitability. There was no significant correlation between sensitivity...
At the neuromuscular junction, several endogenous substances have been shown to act presynaptical... more At the neuromuscular junction, several endogenous substances have been shown to act presynaptically to modify transmitter release. Here we show that angiotensin 1-7, a vasoactive peptide of the renin-angiotensin system, increased quantal content in a dose-dependent manner, with a maximal increase of 78% at 250 nM. At the same dose, angiotensin 1-7 increased paired pulse facilitation by 70%. This is the first report of angiotensin 1-7 altering a cholinergic synapse.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by... more Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by chorea, incoordination and psychiatric and behavioral symptoms. The leading cause of death in HD patients is aspiration pneumonia, associated with respiratory dysfunction, decreased respiratory muscle strength and dysphagia. Although most of the motor symptoms are derived from alterations in the central nervous system, some might be associated with changes in the components of motor units (MU). To explore this hypothesis, we evaluated morphofunctional aspects of the diaphragm muscle in a mouse model for HD (BACHD). We showed that the axons of the phrenic nerves were not affected in 12-months-old BACHD mice, but the axon terminals that form the neuromuscular junctions (NMJs) were more fragmented in these animals in comparison with the wild-type mice. In BACHD mice, the synaptic vesicles of the diaphragm NMJs presented a decreased exocytosis rate. Quantal content and quantal size were sma...
Substance P modulates ion channels and the excitability of sensory neurons in pain pathways. With... more Substance P modulates ion channels and the excitability of sensory neurons in pain pathways. Within the heterogeneous population of Dorsal Root Ganglia (DRG) primary sensory neurons, the properties of cells that are sensitive to Substance P are poorly characterized. To define this population better, dissociated rat DRG neurons were tested for their responsiveness to capsaicin, ATP and acid. Responses to ATP were classified according to the kinetics of current activation and desensitization. The same cells were then tested for modulation of action potential firing by Substance P. Acid and capsaicin currents were more frequently encountered in the largest diameter neurons. P2X3-like ATP currents were concentrated in small diameter neurons. Substance P modulated the excitability in 20 of 72 cells tested (28%). Of the Substance P sensitive cells, 10 exhibited an increase in excitability and 10 exhibited a decrease in excitability. There was no significant correlation between sensitivity...
At the neuromuscular junction, several endogenous substances have been shown to act presynaptical... more At the neuromuscular junction, several endogenous substances have been shown to act presynaptically to modify transmitter release. Here we show that angiotensin 1-7, a vasoactive peptide of the renin-angiotensin system, increased quantal content in a dose-dependent manner, with a maximal increase of 78% at 250 nM. At the same dose, angiotensin 1-7 increased paired pulse facilitation by 70%. This is the first report of angiotensin 1-7 altering a cholinergic synapse.
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