Neuromuscular Physiology and pharmacology Flashcards
Describe resting membrane potential and changes associated with hyper and hypokalemia
Continuously open (leaking) K+ channels on the surface membrane of the neuron permit outward diffusion of K+ down concentration gradient. This results in the extracellular surface of the membrane being lined by positively charged K+ ions while the inside of the membrane becomes lined by negatively charged membrane proteins. Resting membrane potential in excitable tissues (neurons, skeletal muscle, cardiac, etc..) is determined by K+
The typical neuron has a resting membrane potential of -70mv
Acute hyperkalemia reduces the outward diffusion of K+ Because the concentration gradient is smaller. This results in the resting potential being diminished ie. -60mv (the cell depolarizes)
Acute hopykalemia increases the outward diffusion of K+ because the concentration gradient is greater. Therefore,the resting membrane potential is increased ie. -80mv (the cell is hyperpolorized)
Describe the sequence of events of action potential propagation
When depolarization threshold is reached:
A. Na+ channels opens -> Na+ rushes into cell making interior of cell temporarily positively charge relative to the exterior of cell
B. the Na+ channel shuts in the INACTIVATED configuration
C. K+ channels open -> K+ rushes out of the cell restoring electronegativety to the resting level (membrane repolorizes)
D. When the membrane repolorizes the Na+ channels return to original configuration, the activated state.
E. After the action potential has passed, the Na-K-ATPase pump extrude Na and recapture K thereby restoring elyte balance
Describe the significance of the inactivated state of the Na+ channel.
Give 3 clinical examples of this concept
When the fast voltage-gated Na+ channel is in the inactivated state another action potential cannot be fired -> Absolute Refractory period
1) The high K+ concentration in cardioplegia solution causes membrane depolarization, which “locks” Na+ channels in inactivated state so the heart electrically arrests
2) Succinylcholine causes the Na+ channels to lock in the inactivated state thereby electrically arresting skeletal muscle
3) Local anesthetics interrupt nerve conduction by locking the Na+ channels in the inactivated state
What ion is responsible for membrane depolarization?
What ion is responsible for membrane repolorization?
Diffusion of Na+ into the cell is responsible for depolarization (increasing positive charge inside the cell)
Diffusion of K+ out of the cell is responsible for repolarization (increasing positive charge outside the cell)
What is most responsible for resting membrane potential?
Potassium efflux via “leaking” channels
Describe the innervation of skeletal muscles
Efferent motor nerves exit the anterior (ventral) horn of the spinal cord to skeletal muscle
Afferent sensory nerves enter the posterior (dorsal) horn of the spinal cord from skeletal muscles
Describe the anatomy of the neuromuscular junction
The terminal of the motor nerve releases Ach into the motor end plate. Nicotinic receptors and Calcium ion channels are present on the presynaptic membrane. Nicotinic receptors are also present on the postsynaptic membrane with AchE found close by to metabolize Ach
Describe Neuromuscular transmission
1) Motor nerve AP arrives and depolarizes nerve terminal
2) Ca channels open causing Ca to rush into cell
3) The increased intracellular Ca cause vesicles of Ach to fuse to the presynaptic membrane spilling Ach in the synaptic cleft
4) Nicotinic receptors in the presynaptic cleft respond to Ach by increasing production and release of Ach (positive feedback-loop). This prevents depletion of Ach at neuromuscular junction
5) Ach diffuses down concentration gradient and attaches to postsynaptic nicotinic receptors , when both alpha subunits are occupied the Na+ ion channels open
6) Na and Ca diffuse into cell while K defuses out causing depolarization of motor end plate
7) When depolarization reaches threshold an AP is initiated
8) AP sweeps across muscle causing contraction
9) AchE breaks down Ach. As Ach is metabolized the motor end-plate repolarizes and muscle is ready for another AP
10) Ach is broken down into choline and acetate, choline is transported back into presynaptic terminal for Ach synthesis
How does hypo/hypercalcemia and hypo/hypermagnesemia effect release of neuro transmitter?
Hypercalcemia and hypomanesemia are associated with and increase in neurotransmitter release
Hypocalcemian and hypermagnesemia are associated with a decrease in neurotransmitter release
Calcium and magnesium are antagonistic at the nerve terminal (presynaptically)
Metabolism is the primary route of elimination for which neuromuscular blocker(s)?
Succinylcholine (Anectine)
Atracurium (Tracurium)
Cisatracurium (Nimbex)
Mivacurium (Mivacrom)
Billiary excretion is the primary route of elimination for which neuromuscular blocker(s)?
Vecuronium (Norcuron)
Rocuronium (Nimbex)
Renal excretion is the primary route of elimination for which neuromuscular blocker(s)?
D-tubocurarine (Tubarine) Metocurine (Metabine) Pancuronium (Pavulon) Gallamine (Flaxedil) Doxacurium (Nuromax) Pipercurium (Arduan)
Because all muscle relaxants are 100% ionized at physiologic Ph ALL agents can be excreted by the kidneys if other routs are unavailable
Which NMBs have an effect on the autonomic ganglia?
Succinylcholine: modest stimulation
d-Tubocurarine and Metocurine: block nicotinic receptors at the autonomic ganglia
Which NMBs produce bradycardia and why?
Succinylcholine produces bradycardia by mimicking the action of Ach at the muscarinic receptors in the sinoatrial node
Which NMBs cause the release of histamine?
Succinylcholine Mivacurium Atracurium d-Tubocurarine Metocurine
