The delay in recovery from fast inactivation in skeletal muscle sodium channels is deactivation.
1. Using macropatch techniques, we tested the assumption that deactivation underlies the observed delay in the onset to recovery from fast inactivation by comparing open-state deactivation to recovery delay for rat skeletal muscle mutations R1441C and R1441P. 2. Deactivation kinetics from the open state were determined from the exponential decay of tail currents. R1441C and R1441P prolonged open-state deactivation, with the greatest effect produced by R1441P. 3. Delays in the onset to recovery from fast inactivation for R1441P and for R1441C were abbreviated compared to those for rSkM1. Recovery delay was longer in R1441P than R1441C at voltages more negative than -110 mV. Recovery from inactivation exhibited a voltage dependence which, unlike delay, saturated at depolarized voltages. Recovery rate constants were increased to a similar extent for R1441C and R1441P at -150 to -120 mV compared to rSkM1. 4. These results indicate that the delay in the onset to recovery from fast inactivation in skeletal muscle sodium channels is due to deactivation. Lessening of charge immobilization for R1441C and R1441P may contribute to observed biophysical defects underlying the hyperexcitability of muscle fibers containing paramyotonia congenita mutations. The second stage of recovery from fast inactivation may be affected differentially by these mutations.
Groome
J R
JR
Department of Biology, Harvey Mudd College, Claremont, California 91711, USA.
Fujimoto
E
E
Ruben
P C
PC
D000818:Animals; D007700:Kinetics; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism* / Q000503:physiopathology; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D020967:Myotonic Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D009865:Oocytes; D018408:Patch-Clamp Techniques; D011930:Reaction Time / Q000235:genetics*; D020127:Recovery of Function / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism; D013997:Time Factors; D014981:Xenopus
D015222:Sodium Channels