OBJECTIVE: Physiopathology of critical illness polyneuromyopathy was investigated in several animal-based models. Electrophysiologic approach was achieved in denervated and corticosteroid-induced myopathy; other models based on sepsis or inflammatory factors (zymosan, cytokines) were also used but did not consider voltage-gated sodium channel implication in neuromuscular weakness. We have studied electrophysiologic effects of chronic sepsis on an intact neuromuscular rat model with special consideration to the subtypes of sodium channels involved. DESIGN: Experimental animal study. SETTING: University laboratory. SUBJECTS: Wistar rats. INTERVENTIONS: Chronic sepsis was achieved by a technique of cecal ligature and needle perforation. Ten days after surgery, the rats were killed. Fast-twitch flexor digitorum brevis was excised and dissociated in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid-buffered saline supplemented with 3.0 mg/mL collagenase. Fast sodium currents were recorded by a macropatch clamp technique at room temperature (22+/-2 degrees C) in a cell-attached configuration. MEASUREMENTS AND MAIN RESULTS: A decrease in maximal sodium current and in conductance was evidenced without modification of the sodium Nernst potential. A shift of the voltage inactivation curve toward more negative potentials could explain the observed decrease in excitability. In parallel, we observed an up-regulation of NaV 1.5-type sodium channels. CONCLUSIONS: Chronic inflammation and sepsis induced modifications of sodium channel properties that could contribute to muscular inexcitability. This inexcitability can be elicited by a modification of properties or type of voltage-gated sodium channels. Our results lead us to explain this inexcitability by an up-regulation of NaV 1.5 sodium channel.
OBJECTIVE: Physiopathology of critical illness polyneuromyopathy was investigated in several animal-based models. Electrophysiologic approach was achieved in denervated and corticosteroid-induced myopathy; other models based on sepsis or inflammatory factors (zymosan, cytokines) were also used but did not consider voltage-gated sodium channel implication in neuromuscular weakness. We have studied electrophysiologic effects of chronic sepsis on an intact neuromuscular rat model with special consideration to the subtypes of sodium channels involved. DESIGN: Experimental animal study. SETTING: University laboratory. SUBJECTS:Wistar rats. INTERVENTIONS:Chronic sepsis was achieved by a technique of cecal ligature and needle perforation. Ten days after surgery, the rats were killed. Fast-twitch flexor digitorum brevis was excised and dissociated in 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid-buffered saline supplemented with 3.0 mg/mL collagenase. Fast sodium currents were recorded by a macropatch clamp technique at room temperature (22+/-2 degrees C) in a cell-attached configuration. MEASUREMENTS AND MAIN RESULTS: A decrease in maximal sodium current and in conductance was evidenced without modification of the sodium Nernst potential. A shift of the voltage inactivation curve toward more negative potentials could explain the observed decrease in excitability. In parallel, we observed an up-regulation of NaV 1.5-type sodium channels. CONCLUSIONS:Chronic inflammation and sepsis induced modifications of sodium channel properties that could contribute to muscular inexcitability. This inexcitability can be elicited by a modification of properties or type of voltage-gated sodium channels. Our results lead us to explain this inexcitability by an up-regulation of NaV 1.5sodium channel.
Authors: O Friedrich; M B Reid; G Van den Berghe; I Vanhorebeek; G Hermans; M M Rich; L Larsson Journal: Physiol Rev Date: 2015-07 Impact factor: 37.312