Test 2: lecture 19 voltage gates ion channel drugs Flashcards
positive in causes
depolarization
excitatory
positive out of cell causes
hyperpolarization
inhibitory
K out or Cl in
N-type voltage dependent Ca channels are found where?
on neurons
important for release of neurotransmitters
L-type voltage dependent Ca channels are found where?
on cardiac cells
important for action potential in cardiac cells
ion current is dependent on what two things
amount of channels open
electrochemical potential (what is the difference between the inside and outside of cell of a certain ion)
volatge gated ion channels close —
spontaneously - becomes inactivated
will stay closed until next repolarization
ion current is transient
what is modulated receptor hypothesis of voltage gated ion channels
channel can be in one of three states depending on membrane potential
how does voltage gated ion channel change form inactivated to closed state
cell must go through repolarization
what is use dependence of VGIC
effect of drug depends on the channel’s activity or state
drug works better if channels are open and drug can get into cell and bind to intracellular bind site
what is state dependence of drugs for VGIC
certain drugs have affinity for ion channels in different states (open, resting, inactive)
what does this show
use and state dependence of a drug, that the more the channels opens the more drug gets inside and causes a block/decrease of the sodium current
how can a drug change the gating behavior
can make it easier or harder for impulse to cause channel to open
how do local anesthetics work
block voltage gated Na channels on the nocicpetors- specialized neurons that respond to pain stimuli
blocks pain stimuli signal
— are specialized neurons that respond to pain stimuli
nociceptors
you can block pain impulse by blocking the VG Na channels with local anesthetics
local anesthetics block initiation and propagation of AP by blocking —
VG Na channels
attach on inside of channel pore → needs to get into cell to work
local anesthetics bind to what state of VG Na channels?
will bind to all three states but prefers intacte state
results in very slow change from inactive to closed during repolarization= prologoned refractory period
how does pH effect how lidocaine gets into cell
high pH/ basic extracellular will make ↑ unprotonated lidiocaine, which can penetrate membrane and get into cell
the inside of the cell is more acidic
low pH/acidic= ↑ protonated lidocaine which will bind to channel
extracellular pH is more acidic in tissues under infection- this will decrease permability of lidocaine
infection will do what to pH of an area?
how will this effect lidocaine?
infection causes more acidic environment
this leads to more protonated lidocaine in the extracellular space, protonated lidocaine can NOT get into cell to work
infection will slow/stop permeability, will need to use more drug to be effective
local anesthetics (lidocaine) binds to what state of VG Na channels on nociceptors
all three but binds more strongly to inactive and/or open then closed state
class I antiarrhthmic drugs block what channels
voltage gated Na channels
many antiarrhythmic drugs will show a use dependence for —state of VG NA channels
open and/or inactive
will block high frequency excitation= tachycardiac or premature beats
also blocks depolarized/injured tissue preferentially, these channels are in the inactive state
Class I antiarrhythmic drugs are classified by how quickly they — the sodium channel
dissociate/unbind
if drug unbinds quickly: have stronger activity during high rates of depolarization (tachycardia)
if drug unbinds slowly: there is an accumulation of block
lidocaine will unbind — from the VG Na channels in the heart
quickly- will have stronger activity during high rates of depolarization (tachycardias)
quinidine will undind — flow VG Na channels in the heart
slowly leads to accumulation of block
some anticonvulsants such as — work as Na channel blockers. Block is strongest when nerves fire at high frequency (during convulsions/seizures)
dilantin (phenytoin)
how does grayanotoxins work
will stabilize open conformation of VG Na channels
too much Na into cell
can be found in rhododendrons and azaleas, can be in unpasteurized honey of bees that feed off these plants
indirect method of opening VG Ca channels
will act on β adrenergic receptors(G protein receptor) in cardiac muscle and cause down stream activation that leads to increase in cAMP kinase, ⍺ subunit will also bind to calcium channel
this will increase the probability of Ca channel opening at any given volatage
inotopic β-adrenergic effect
nifedipine(dihydropyridine) binds to the — state of the VG Ca channel
resting
verapamil ( phenylalkylamine) binds to the — state of the VG Ca channel
open
diltiazem(benzothiazepine) binds to the — state of the VG Ca channel
inactivated
antagonist VG Ca channel drugs such as diltiazem will do what ?
will lower the amount of calcium into a cell
Cardiovascular implications
* Decreased sinoatrial (SA) node pacemaker rate
* Decreased atrioventricular (AV) node conduction velocity
* Reduced cardiac muscle contractility
* Vascular smooth muscle relaxation
Nifedipine: binds to the RESTING state
Verapamil: binds to the OPEN state
Diltiazem: binds to the INACTIVATED state
Nifedipine, Verapamil, Diltiazem act as — on — channel drugs
antagonists
L-type Ca channels in the heart
Calcium channel blocker drugs: will cause decrease of Ca into a cell, which leads to slower NR, reduced cardiac output/contraction, will cause relaxation/dilation of vascular smooth muscle
used to stop supraventricular tachycardias
Calcium channel blockers will do what to blood pressure
will cause arteriole dilation → decrease in BP
Nifedipine is a more potent vasodilator, has stronger affinity for Ca channels on smooth muscle then L type Ca channel on the heart like verapamil and diltiazem
unwanted side effects of Ca channel blockers
other type of smooth muscle can relax
headaches and flushing
constipation
AV block and negative inotropic effects
what does cantharidin do?
toxin in blister beetles
will cause Calcium channels to open leading to increased contractions/activation of cells
horses very susceptible- can die within 24-74 hrs
