DAT with Na+ channel blocking via Na+/K+ ATPase pump mechanics

[Nagelfar]

If sodium ions must bind to the DA transporter before DA binds to DAT, might the sodium pump's intracellular Na+ concentration gradient be affected by an intracellular Na+ channel blocker in such wise that the DAT neuron depolarizes to release DA? Also might traditional releasing agents be said to make DAT alter it's function to an antiporter in its mechanism of release, whereas release by neuron depolarization wouldn't, leaving its symporter method of action unchanged by contrast. (and might cocaine's anaesthetic be theorized to function in conjunction to its DAT ligand affinity in such a way?)

 

[airsh0w]

If sodium ions must bind to the DA transporter before DA binds to DAT, might the sodium pump's intracellular Na+ concentration gradient be affected by an intracellular Na+ channel blocker in such wise that the DAT neuron depolarizes to release DA?

A sodium blocker will prevent depolarization by keeping the charge positive. A sodium blocker blocks the channels which are responsible for the depolarization of a neuron. The sodium bonds on the outside of the cell. The intracelluar concentration would be lowered by a sodium blocker causing a more negative intracelluar concentration gradient decreasing the chance of an action potential.

Also might traditional releasing agents be said to make DAT alter it's function to an antiporter in its mechanism of release, whereas release by neuron depolarization wouldn't, leaving its symporter method of action unchanged by contrast. (and might cocaine's anaesthetic be theorized to function in conjunction to its DAT ligand affinity in such a way?)

Yes depolarization uses vesicles; it doesn't reverse the transporter. Cocaine does block intracellular sodium channels as a local anesthetic. They aren't apparently related though. Cocaine binds to the pump and to the DAT causing the effects.

 

[Nagelfar]

A sodium blocker will prevent depolarization by keeping the charge positive. A sodium blocker blocks the channels which are responsible for the depolarization of a neuron. The sodium bonds on the outside of the cell. The intracelluar concentration would be lowered by a sodium blocker causing a more negative intracelluar concentration gradient decreasing the chance of an action potential.

So might an anesthetic, acting to 'prevent depolarization' elsewhere along the channels, cause a build-up to an eventual depolarization 'all at once' if it is also a DRI and attaches as a ligand to DAT? I've read membrane polarity "dramatically" influences transport rates so the specific profile of intense subjective rush.

It is a question I've had on that issue due to cocaine's sodium blocking ability, I know that pure anesthetics by routes that aren't topical cause more stimulation in cocaine experienced mice than placebo, for instance.

Yes depolarization uses vesicles; it doesn't reverse the transporter. Cocaine does block intracellular sodium channels as a local anesthetic. They aren't apparently related though. Cocaine binds to the pump and to the DAT causing the effects.

My question here is on DRAs like amphetamine; if the reversal of transporters is analogous to function as antiporters (allowing re-entry of dopamine into DAT being the same) and if the same mechanisms of action applies to that of antiporters over symporters. If that is the case, i.e. neuron depolarization contributed to release, then would only the symporter comformation of the transporter (the native state of the transporter) add to the build-up of dopamine in the synapse if the re-uptake were blocked because the anti-porter type gate would allow dopamine to re-enter (as done in DRAs like methamp)?