Fast- or Slow-inactivated State Preference of Na+ Channel Inhibitors: A Simulation and Experimental Study
Author Summary
Sodium channels are the key proteins for action potential firing in most excitable cells. Inhibitor drugs prevent excitation (local anesthetics), regulate excitability (antiarrhythmics), or prevent overexcitation (antiepileptic, antispastic and neuroprotective drugs) by binding to the channel and keeping it in one of the inactivated channel conformations. Sodium channels have one fast- and several slow-inactivated conformations (states). The specific stabilization of slow-inactivated states have been proposed to be advantageous in certain therapeutic applications. The question of whether individual drugs stabilize the fast or the slow-inactivated state is studied using specific voltage protocols. We tested the reliability of conclusions based on these protocols in simulatio...
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