succinylcholine mechanism of action Q

[cfdavid]

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Gents,

We're being introduced to cholinergic pharm right now. I have a question regarding "Phase I Depolarizing blockade". I just want to be sure that I clearly understand this mechanism.

According to our notes, when SuCh binds AChR's there's a brief period of depolarization that can cause fasciculations. However, once equillibrium sets in, the action of SuCh is such that the RMP is moved closer to zero.

(Here's where I feel our notes are lacking). It explains the fact that with the new RMP of zero, any constitutive release of ACh can not initiate an AP.
No problem there.

However, mechanistically, my question is this... At RMP=0 is it the fact that there simply is no longer a driving force for Na+ to rush into the cell that causes this "inaction"??

Our notes go on to suggest that stimulation of motor nerves at this time will further decrease the potential difference, and thus would intensify the phase I depolarized blockade.

Is the deal that since the RMP has already exceeded (for a prolonged period of time) the traditional threshold of -40 mV (via SuCh), any minor inrush of Na+ at the new RMP of 0 simply will not cause an AP for some reason, but would rather intensify the blockade by further increasing the RMP to a more positive #????

And if so, wouldn't this depolarization be enough to open V-gated Ca2+ channels, thereby causing a contraction anyway??


Any clarification would be great.

Thanks,

cf

 

[aredoubleyou]

Ach opens the Na chanel gate, so does Sch. After a short while the gate closes. Ach is degraded, the chanel returns to its normal resting potential and can be opened again with the next repolorization. With Sch the channel continues to be depolarized and the gate (which closes on its own) cannot be returned to its normal resting position until the stimulus is removed. It might not be exactly how it works, but I try keeping things simple

 

[amyl]

like RW said, more detail if you want it: there are two gates on Na channel... ions can only pass when both are open. upper gate is voltage dependent and the lower (aka inactivation) gate is time dependent. at rest lower gate is open and other is closed. depolarization opens upper gate and then Na passes. after some time the lower gate closes and doesn't open back up until the membrane repolarizes... this doesn't happen while SCh is in the receptor.
prolonged end plate depolarization in this manner causes changes in the receptor itself and this is phase two block.
help?