Sodium channel activation mechanisms. Insights from deuterium oxide substitution

Journal Article · Sun Apr 01 00:00:00 EST 1990 · Biophysical Journal; (USA)

DOI:https://doi.org/10.1016/S0006-3495(90)82595-9· OSTI ID:6695296

Alicata, D A; Rayner, M D; Starkus, J G ^[1]

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1. Pacific Biomedical Research Center, Honolulu, HI (USA)

Schauf and Bullock, using Myxicola giant axons, demonstrated that solvent substitution with deuterium oxide (D2O) significantly affects both sodium channel activation and inactivation kinetics without corresponding changes in gating current or tail current rates. They concluded that (a) no significant component of gating current derives from the final channel opening step, and (b) channels must deactivate (during tail currents) by a different pathway from that used in channel opening. By contrast, Oxford found in squid axons that when a depolarizing pulse is interrupted by a brief (approximately 100 microseconds) return to holding potential, subsequent reactivation (secondary activation) is very rapid and shows almost monoexponential kinetics. Increasing the interpulse interval resulted in secondary activation rate returning towards control, sigmoid (primary activation) kinetics. He concluded that channels open and close (deactivate) via the same pathway. We have repeated both sets of observations in crayfish axons, confirming the results obtained in both previous studies, despite the apparently contradictory conclusions reached by these authors. On the other hand, we find that secondary activation after a brief interpulse interval (50 microseconds) is insensitive to D2O, although reactivation after longer interpulse intervals (approximately 400 microseconds) returns towards a D2O sensitivity similar to that of primary activation. We conclude that D2O-sensitive primary activation and D2O-insensitive tail current deactivation involve separate pathways. However, D2O-insensitive secondary activation involves reversal of the D2O-insensitive deactivation step. These conclusions are consistent with parallel gate models, provided that one gating particle has a substantially reduced effective valence.

• OSTI ID: 6695296
• Journal Information: Biophysical Journal; (USA), Vol. 57:4; ISSN 0006-3495
• Country of Publication: United States
• Language: English

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