Montemayor DSA Flashcards
Voltage-gated sodium channel- ways of being
Closed but capable of opening (activation gate- M gate- closed; Inactivation gate- h gate- open)
Open- rapid opening triggered at threshold
Closed- with inactivation gate
May I get in? Hell no. (H gate)
potassium gates are open when?
from peak potential through
after hyperpolarization
Dependence of RMP on Extracellular K+ Concentration **
ECF [K+] affects membrane excitability
Insulin, epinephrine, aldosterone promote cellular uptake of K+
Deficiencies may result in hyperkalemia
Cell death may result in hyperkalemia
Potassium’s Contribution to the Resting Membrane Potential
↑ K+ conductance:
- ↑ K+ efflux (membrane potential becomes more negative, or hyperpolarized)
↓ ECF [K+] (Hypokalemia):
- ↑ K+ efflux
(membrane potential becomes more negative, or hyperpolarized)
↑ ECF [K+] (Hyperkalemia):
- ↓ K+ efflux (or promote K+ influx) (membrane potential becomes less negative, depolarized)
** Key: Resting membrane potential is very sensitive to changes in ECF [K+]
Synaptic transmission
Neurotransmitter molecules are synthesized and packaged in vessels
An action potential arrives at the presynaptic terminal
voltage-gated Ca2_ channels open, Ca2+ enters
A rise in Ca2+ triggerrs fusion of synaptic vesicles with the postsynaptic membrane
Transmitter molecules diffuse across the synaptic cleft and bind to specific receptors on the postsynaptic cell
Bound receptors activate the postsynaptic cell
A neurotransmitter breaks down, is taken up by the presynaptic terminal or other cells or diffuses away from the synapse
Chemical Synapse: Neurotransmitters carry signal across synapse to postsynaptic receptors
AP at axon terminal of presynaptic neuron opens voltage-gated Ca2+ channels
Ca2+ influx from ECF into synaptic knob
Ca2+ influx induces fusion & exocytosis of synaptic vesicles → neurotransmitter into the synaptic cleft
N.T.s diffuse & bind to receptors on subsynaptic membrane of the postsynaptic neuron
Bound N.T.s result in alteration of membrane permeability of postsynaptic neuron
Termination of signal by removal of N.T. from synaptic cleft (enzymatic breakdown, cellular uptake, diffusion)
Neuromuscular Junction
Specialized Synapse Between Motor Neuron & Skeletal Muscle Fiber
An axon typically synapses at a single point (NMJ or end plate), midway along the length of a skeletal muscle fiber.
NMJ Structure
- Active Zones:
Area for fusion of synaptic vesicles & release of ACh
- Clustering of synaptic vesicles
Above secondary postsynaptic clefts between adjacent postjunctional folds
- Postjunctional Folds:
Increase surface area of muscle plasma membrane
Invaginations on postsynaptic membrane opposite nerve terminal - Synaptic cleft:
~ 50 nm, time delay in impulse transmission with ACh diffusion - Nicotinic Acetylcholine Receptors:
High density expression at crests of postjunctional folds
5. Acetylcholinesterase (AChE):
High concentration
associated with synaptic
basal lamina
(basement membrane)
Terminates synaptic
transmission after AP
Nerve terminal: Site of ACh synthesis and uptake by vesicles
Choline acetyltransferase:
Synthesizes ACh from choline + acetyl coenzyme A
ACh-H+ exchanger:
ACh uptake by synaptic vesicle
Driven by vesicular proton electrochemical gradient
Synaptic Vesicle Membrane Proteins
- Synaptobrevin: (v-SNARE)
Essential for transmitter release
Forms complex with SNAP-25 & syntaxin (presynaptic membrane proteins; t-SNAREs)
Helps drive vesicle fusion
- Synaptotagmin:
Ca2+ receptor of synaptic vesicle
Detects rise in [Ca2+]i and triggers
exocytosis of docked vesicles
Vesicle Fusion
- & 4. Syntaxin & SNAP-25 (t-SNARES)
Presynaptic membrane of nerve terminal; key role in fusion process
Synaptobrevin coils around free ends of syntaxin/SNAP-25, bringing the vesicle closer to the presynaptic membrane
Exocytosis
Synaptotagmin: [Ca2+]i sensor
Ca2+ enters through voltage-gated Ca2+ channels near the active zone of the presynaptic membrane
Triggers vesicle fusion and exocytosis
Neurotoxins That Block Fusion of Synaptic Vesicles
- Tetanus toxin and botulinum toxins B, D, F, and G: endoproteinases act on synaptobrevin
- Botulinum toxins A and E: cleave SNAP-25
- Botulinum toxin C1: cleaves syntaxin
ACh Receptor
Permeable to cations (ex: Na+, K+, & Ca2+)
Current of Ca2+ is minimal and is ignored
Na+ and K+ become equally permeable
Result: increase the normally low (resting) permeability of Na+ relative to K+ →
Vm shifts to a value between EK (−80 mV) and ENa (+50 mV)
End-plate Potential = graded potential of end plate, small depolarization
Termination of Neurotransmitter Action
Acetylcholinesterase (AChE)
Enzymatic degradation removes ACh from synaptic cleft of cholinergic synapses
AChE hydrolyzes ACh to choline + acetate (2 steps)
