Abstract
The actions of phenytoin (DPH) on sodium channels of squid giant axons were investigated. DPH suppressed the sodium current whether it was applied internally or externally. When DPH was applied externally, its potency depended upon the pH of the external solution. Similarly, when DPH was applied internally, its potency depended on the pH of the internal solution. The potency of DPH increased when the pH of the solution was lowered and the potency was relatively insensitive to pH changes in the solution on the opposite side of the membrane. These results suggest that the weak acid DPH, that exists at physiological pH values in both anionic and neutral forms, acts as a neutral molecule. Our results are reasonably well described by a model wherein one neutral DPH molecule interacts with and blocks one sodium channel. We find an equilibrium constant for the interactions with normal axons to be about 57 microM.
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|
Log in using your username and password
Purchase access
In this issue
Determination of the active form of phenytoin.
