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- Title
Inactivation of sodium channels underlies reversible neuropathy during critical illness in rats.
- Authors
Novak, Kevin R.; Nardelli, Paul; Cope, Tim C.; Filatov, Gregory; Glass, Jonathan D.; Khan, Jaffar; Rich, Mark M.
- Abstract
Neuropathy and myopathy can cause weakness during critical illness. To determine whether reduced excitability of peripheral nerves, rather than degeneration, is the mechanism underlying acute neuropathy in critically ill patients, we prospectively followed patients during the acute phase of critical illness and early recovery and assessed nerve conduction. During the period of early recovery from critical illness, patients recovered from neuropathy within days. This rapidly reversible neuropathy has not to our knowledge been previously described in critically ill patients and may be a novel type of neuropathy. In vivo intracellular recordings from dorsal root axons in septic rats revealed reduced action potential amplitude, demonstrating that reduced excitability of nerve was the mechanism underlying neuropathy. When action potentials were triggered by hyperpolarizing pulses, their amplitudes largely recovered, indicating that inactivation of sodium channels was an important contributor to reduced excitability. There was no depolarization of axon resting potential in septic rats, which ruled out a contribution of resting potential to the increased inactivation of sodium channels. Our data suggest that a hyperpolarized shift in the voltage dependence of sodium channel inactivation causes increased sodium inactivation and reduced excitability. Acquired sodium channelopathy may be the mechanism underlying acute neuropathy in critically ill patients.
- Subjects
ALTERNATIVE medicine; CRITICAL care medicine; PHYSIOLOGICAL transport of sodium; ION channels; HUMAN heredity; NEURAL conduction; ACTION potentials; BIOLOGICAL transport; CELL membranes; ANIMALS; CATASTROPHIC illness; DEGENERATION (Pathology); ELECTROLYTES; ELECTROMYOGRAPHY; BIOELECTRIC impedance; MEMBRANE proteins; MOTOR neurons; MUSCLE diseases; PERIPHERAL neuropathy; POLYNEUROPATHIES; RATS; SENSORY receptors; SEPSIS; MUSCLE weakness; DISEASE complications; PHYSIOLOGY
- Publication
Journal of Clinical Investigation, 2009, Vol 119, Issue 5, p1150
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI36570