simi
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phenytoin blocks axonal Na channels in their inactivated state..i.e state or rate dependent blockade...i know what is state dependent..can anyone explain what is rate dependent blockade plzzz
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| po
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dint know the diff till now,
The drugs blocked Na+ currents in both a tonic and use[rate]-dependent manner.
Tonic block was more pronounced at depolarized holding potentials and reduced at hyperpolarized membrane potentials, reflecting an overall negative shift in the relationship between membrane potential and steady state inactivation. Dose-response relationships with phenytoin supported the hypothesis that the voltage dependence of tonic block resulted from the higher affinity of the drugs for inactivated than for resting channels.
The use-dependent component of block developed progressively during a 2-Hz train of 40-msec-long stimulus pulses from -85 mV to 0 mV. At 2 Hz, verapamil was the most potent use-dependent blocker, lidocaine and phenytoin had intermediate potencies, and carbamazepine was least effective. The use-dependent block resulted from drug binding to open and inactivated channels during the depolarizing pulses and the slow repriming of drug-bound channels during the interpulse intervals. Verapamil, lidocaine, and phenytoin all bound preferentially to open channels, but this open channel block was most striking for verapamil. Use-dependent block was less pronounced at hyperpolarized membrane potentials, due to more rapid repriming of drug-bound channels.
http://www.ionchannels.org/showabstract.php?pmid=...
some more info on use[rate]dependant-
http://lysine.pharm.utah.edu/netpharm/netpharm_98...(rate)-Dependent%20Blockade%20by
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| simi
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thanks alot po...i took a lot of time to understand...but the concept is not very clear to me...guess i have to read some big book.!
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| new_n_lost
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i m going to give it a try as wht i had understood when i read the Rate Dependent Blockade.
Rate Dependent or Use Dependent r one and the same thing.
Any Drug which blocks a Channel while it is not in its Resting state wud be termed as Use Dependent or Rate Dependent i.e If the Sodium channel is open and the drug blocks it then its called Rate Dependent cos its effecting the blockade when the Sodium channels r open not when the channels r closed. thus in effect wht is meant here is that Drugs which act during the Depolarization of the cell r termed as Rate Dependent.
The three normal channel states are: Resting, Open (or Activated), and Inactive
Under normal resting (polarized) conditions, the sodium channels are predominantly in the Resting state and are nonconducting
When the membrane is depolarized, the sodium channels Open and conduct sodium, resulting in the inward sodium current that makes the major contribution to phase 0 of the action potential
The inward sodium current rapidly decays as channels move to the Inactive state
The return of the Inactive channel to the Resting state is termed reactivation and is voltage- and time-dependent.
The theory assumes that channel blocker drugs bind different channel states with different affinities and that drug binding alters the transition rates between different states
Drug binding results in transitions to R*, O*, and I* , channel states which have different transition rates between states than the normal channel states
The most clinically useful drugs would have affinity for the Open and/or Inactive state, and thereby exhibit use-dependent blockade
Drugs with high affinity for the Resting state would be toxic
Here is a Link which helped me a lot while understanding this concept.
http://lysine.pharm.utah.edu/netpharm/netpharm_00...(rate)-Dependent%20Blockade%20by
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| simi
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thanks alot NNL..that was a simple n nice explanation...in the beginning i thought ..state dependent n rate dependent r different...so u mean to say...state or rate or use dependent r one n the same...
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| simi
Forum Elite
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and also...Any Drug which blocks a Channel while it is not in its Resting state wud be termed as Use or rate dpendent...that means the channel can be activated(open) or inactivated(close)....so even though the channels r closed in inactivated state...like they r closed in resting state...the drugs acting in inactivated state r rate dependent...is it coz the inactivated stage is still in depolarization phase (refractory)?
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| simi
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sorry for bothering u
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