Neuroscience and Cell Physiology: Fluid Compartments, Membrane Potentials, and Synaptic Transmission

About 2/3 of total body water.

[L1] What fraction of total body water is intracellular fluid (ICF)?

About 1/3 of total body water.

[L1] What fraction of total body water is extracellular fluid (ECF)?

Plasma and interstitial fluid.

[L1] What are the two major parts of extracellular fluid?

Outside cells, in extracellular fluid.

[L1] Where is Na+ found in greatest concentration?

Inside cells, in intracellular fluid.

[L1] Where is K+ found in greatest concentration?

Maintenance of physiological variables in a state of dynamic constancy around a set point.

[L1] What is homeostasis?

A response that opposes a disturbance and moves a variable back toward its set point.

[L1] What is negative feedback?

A response that amplifies the original disturbance, such as uterine contractions during labor.

[L1] What is positive feedback?

Greater resting permeability to K+ through K+ leak channels.

[L1] What mainly creates the resting membrane potential?

Approximately -70 mV, meaning the inside is negative relative to the outside.

[L1] What is a typical resting membrane potential?

3 Na+ out of the cell and 2 K+ into the cell.

[L1] What does the Na+/K+ pump move per ATP?

To maintain the Na+ and K+ concentration gradients across the membrane.

[L1] What is the main purpose of the Na+/K+ pump?

Na+ enters and the membrane depolarizes.

[L1] What happens when Na+ channels open?

K+ leaves and the inside becomes more negative.

[L1] What happens when K+ channels open?

A change in membrane potential that makes the inside less negative or more positive.

[L1] What is depolarization?

A return toward the resting negative membrane potential after depolarization.

[L1] What is repolarization?

The membrane becomes more negative than its resting potential.

[L1] What is hyperpolarization?

A local membrane-potential change whose size depends on stimulus strength and that decreases with distance.

[L1] What is a graded potential?

Graded potentials vary in size, can summate, and decay with distance; action potentials are all-or-none and propagate without decreasing.

[L1] What properties distinguish graded potentials from action potentials?

The amount of depolarization needed to trigger an action potential, often near -55 mV.

[L1] What is threshold?

Voltage-gated Na+ channels open and Na+ enters rapidly.

[L1] What causes the rapid depolarization phase of an action potential?

Na+ channels inactivate while voltage-gated K+ channels open and K+ leaves.

[L1] What causes repolarization during an action potential?

Voltage-gated K+ channels close slowly, allowing extra K+ to leave.

[L1] What causes after-hyperpolarization?

No second action potential can occur because voltage-gated Na+ channels are open or inactivated and have not reset.

[L1] What is the absolute refractory period?

A stronger stimulus can produce an action potential because some Na+ channels have reset but the membrane remains hyperpolarized.

[L1] What is the relative refractory period?

Less K+ leaves the cell, so the membrane depolarizes.

[L1] What happens if extracellular K+ increases?

More K+ leaves the cell, so the membrane hyperpolarizes.

[L1] What happens if extracellular K+ decreases?

The driving force for Na+ entry increases, potentially increasing action-potential spike height.

[L1] What happens if extracellular Na+ increases?

The driving force for Na+ entry decreases, producing a less positive action-potential peak.

[L1] What happens if extracellular Na+ decreases?

Approximately -90 mV.

[L1] What is the equilibrium potential for K+ approximately?

Graded potentials may still occur, but the cell cannot produce the rapid depolarization of an action potential.

[L1 Application] What happens if voltage-gated Na+ channels are blocked?

Repolarization is delayed and the action potential is prolonged.

[L1 Application] What happens if voltage-gated K+ channels are blocked?

A specialized junction between two neurons or between a neuron and another target such as a muscle cell.

[L2] What is a synapse?

Electrical synapses use gap junctions for direct current flow; chemical synapses release neurotransmitters across a synaptic cleft.

[L2] What is the difference between electrical and chemical synapses?

Presynaptic AP arrives; voltage-gated Ca2+ channels open; Ca2+ enters; vesicles fuse; neurotransmitter is released; neurotransmitter binds postsynaptic receptors; a graded potential forms.

[L2] What is the sequence of chemical synaptic transmission?

Ca2+ entering the presynaptic terminal.

[L2] What directly triggers neurotransmitter exocytosis?

In synaptic vesicles in the presynaptic axon terminal.

[L2] Where are neurotransmitters stored before release?

A graded depolarization that moves the postsynaptic cell closer to threshold.

[L2] What is an excitatory postsynaptic potential (EPSP)?

A graded hyperpolarization or stabilization that moves the postsynaptic cell farther from threshold.

[L2] What is an inhibitory postsynaptic potential (IPSP)?

Na+ enters and produces depolarization or excitation.

[L2] How can opening a chemically gated Na+ channel affect a postsynaptic cell?

K+ leaves, making the inside more negative.

[L2] How can opening a chemically gated K+ channel inhibit a postsynaptic cell?

Cl- enters or stabilizes the negative membrane potential, producing inhibition.

[L2] How can opening a chemically gated Cl- channel inhibit a postsynaptic cell?

Produces inhibition and hyperpolarization of the postsynaptic membrane.

[L2] What does GABA usually do?

A substance that binds a receptor and activates or mimics its normal effect.

[L2] What is an agonist?

A substance that binds a receptor and blocks its activation.

[L2] What is an antagonist?

They enhance GABA-related inhibition, producing greater postsynaptic inhibition.

[L2] How do benzodiazepines such as Xanax and Valium act?

They block serotonin reuptake, allowing serotonin to remain in the synaptic cleft longer.

[L2] How do SSRIs act at a synapse?

It blocks reuptake of monoamines such as dopamine, increasing their action in the synaptic cleft.

[L2] How does cocaine act at synapses?

It acts as an agonist at endogenous opioid receptors.

[L2] How does heroin affect the nervous system?

It is an external opioid drug that mimics endogenous opioid signaling.

[L2] Why is morphine not classified as an endogenous neurotransmitter?

Serotonin causes presynaptic Ca2+ channels to remain open longer, increasing neurotransmitter release.

[L2] What is presynaptic facilitation by serotonin?

It destroys SNARE proteins in inhibitory presynaptic terminals, preventing inhibitory neurotransmitter release.

[L2] What is the mechanism of tetanus toxin?

Loss of inhibition causes excessive motor activity, sustained contraction, and spastic paralysis.

[L2] What is the result of tetanus toxin?

It destroys SNARE proteins at excitatory motor terminals, preventing ACh vesicle fusion and release.

[L2] What is the mechanism of botulinum toxin?

Reduced skeletal-muscle stimulation and flaccid paralysis.

[L2] What is the result of botulinum toxin?

A small localized dose of botulinum toxin reduces ACh release and weakens selected muscles or glandular secretion.

[L2] How does Botox work?

Neurotransmitter exocytosis is prevented even if the action potential reaches the terminal.

[L2] What happens if presynaptic Ca2+ channels are blocked?

They block voltage-gated Na+ channels, allowing local graded potentials but preventing action-potential propagation.

[L2] How do procaine or lidocaine affect neurons?

Net movement of particles from higher concentration to lower concentration.

[L3] What is diffusion?

A larger concentration gradient, greater permeability, larger surface area, shorter distance, and higher temperature.

[L3] What factors increase diffusion rate?

Net movement of water across a selectively permeable membrane toward the side with more nonpenetrating solute.

[L3] What is osmosis?

The pressure required to oppose osmosis; it increases as solute concentration increases.

[L3] What is osmotic pressure?

A solution that causes no net water movement and no major change in cell volume.

[L3] What is an isotonic solution?

A solution with lower effective solute concentration than the cell, causing water to enter and the cell to swell.

[L3] What is a hypotonic solution?

A solution with higher effective solute concentration than the cell, causing water to leave and the cell to shrink.

[L3] What is a hypertonic solution?

Water enters; the cell swells and may undergo hemolysis.

[L3] What happens to a red blood cell in a hypotonic solution?

Intracellular osmolarity increases, so water enters and the cell swells.

[L3] What happens to a cell if intracellular nonpenetrating solute increases?

The physical pressure exerted by a fluid, which can oppose osmotic water movement.

[L3] What is hydrostatic pressure?

Endocytosis and exocytosis.

[L3] What are the two major forms of vesicular transport?

Movement of extracellular material into a cell inside vesicles.

[L3] What is endocytosis?

Fusion of intracellular vesicles with the membrane to release material outside the cell.

[L3] What is exocytosis?

Thick filaments are myosin; thin filaments are mainly actin with troponin and tropomyosin.

[L3] What are the thick and thin filaments?

The repeating functional contractile unit of skeletal muscle.

[L3] What is a sarcomere?

Actin, myosin, troponin, and tropomyosin.

[L3] What are the four major skeletal-muscle proteins?

Binds Ca2+ and changes shape, causing tropomyosin to move.

[L3] What does troponin do?

Covers the myosin-binding sites on actin.

[L3] What does tropomyosin do at rest?

Troponin.

[L3] What does calcium bind during skeletal-muscle contraction?

Troponin changes shape, tropomyosin moves, and myosin-binding sites on actin are exposed.

[L3] What happens after Ca2+ binds troponin?

The myosin head.

[L3] Which part of myosin acts as an ATPase?

Thick myosin filaments and thin actin filaments.

[L3] What structures are connected by cross-bridges?

Carry the muscle action potential deep into the center of the muscle fiber.

[L3] What do T-tubules do?

The membrane becomes more permeable to Na+, producing an end-plate depolarization.

[L3] What happens when ACh binds receptors at the motor end plate?

Motor-end-plate depolarization decreases, so muscle contraction is reduced or prevented.

[L3] What happens if muscle nicotinic ACh receptors are blocked?

ACh remains in the cleft and repeatedly stimulates the muscle, causing sustained contraction.

[L3] What happens if acetylcholinesterase is inhibited?

Neuromuscular transmission; muscle excitation; excitation-contraction coupling; cross-bridge cycling; relaxation.

[L4] What are the major stages from motor-neuron signaling to muscle contraction?

Motor-neuron AP; presynaptic Ca2+ entry; ACh release; ACh binds nicotinic receptors; Na+ enters; end-plate potential reaches threshold; muscle AP begins.

[L4] What is the neuromuscular-junction sequence?

Muscle AP travels along sarcolemma and T-tubules; DHPR senses voltage; DHPR activates RyR; SR releases Ca2+; Ca2+ binds troponin; tropomyosin moves.

[L4] What is the excitation-contraction coupling sequence?

The voltage-sensing protein in the T-tubule membrane that activates the ryanodine receptor in skeletal muscle.

[L4] What is DHPR?

The Ca2+-release channel in the sarcoplasmic-reticulum membrane.

[L4] What is the ryanodine receptor (RyR)?

No. DHPR detects voltage and activates RyR.

[L4] Does RyR activate DHPR?

The muscle AP reaches the T-tubule, but little Ca2+ is released from the SR, so contraction is weak or absent.

[L4] What happens if DHPR works but RyR is blocked?

Tropomyosin remains over actin's binding sites and cross-bridges cannot form.

[L4] What happens if Ca2+ cannot bind troponin?

An energized myosin head holding ADP and Pi binds an exposed site on actin.

[L4] What is cross-bridge step 1: attachment?

Pi release triggers the myosin head to pivot and pull actin; ADP is then released.

[L4] What is cross-bridge step 2: power stroke?

A new ATP binds myosin and causes it to release actin.

[L4] What is cross-bridge step 3: detachment?

Myosin hydrolyzes ATP into ADP and Pi, using the energy to recock the head.

[L4] What is cross-bridge step 4: reactivation?

Attach; pull; detach; recock.

[L4] What is the easiest cross-bridge order to remember?

Myosin detaches from actin.

[L4] What happens when ATP binds myosin?

The myosin head becomes energized and recocks.

[L4] What happens when ATP is hydrolyzed by myosin?

Myosin cannot detach and the Ca2+-ATPase pump cannot remove cytoplasmic Ca2+, producing rigor.

[L4] What happens if ATP is unavailable?