Membrane Transport & Excitable Cells

The Synapse: Where Electricity Becomes Chemistry

Synapses are specialized junctions where neurons communicate with other neurons, muscle fibers, or glands. This process is fundamental to nervous system function and muscle contraction.

• Presynaptic neuron: Sends the signal.

• Postsynaptic cell: Receives the signal; can be another neuron, muscle fiber, or gland.

• Types of synaptic arrangements:

  • Axodendritic: Most common, often on dendritic spines.

  • Axosomatic: Onto the cell body.

  • Axoaxonic: Modulates transmitter release from the target terminal.

Electrical vs Chemical Synapses

Neurons communicate via two main types of synapses: electrical and chemical.

• Electrical synapses:

  • Gap junctions directly connect cytoplasm of adjacent cells.

  • Very fast, can be bidirectional.

  • Synchronize activity (e.g., heart, smooth muscle).

• Chemical synapses:

  • Cells separated by a synaptic cleft (30–50 nm).

  • Neurotransmitter released from presynaptic neuron binds to receptors on postsynaptic cell.

  • Slower, but highly modifiable.

Events at a Chemical Synapse

Chemical synaptic transmission involves several steps:

1. Action potential arrives at axon terminal.

2. Voltage-gated Ca2+ channels open; Ca2+ enters.

3. Ca2+ triggers exocytosis of synaptic vesicles.

4. Neurotransmitter diffuses across cleft and binds receptors.

5. Ion channels open, causing a graded postsynaptic potential.

6. Signal ends via reuptake, enzymatic breakdown, or diffusion.

Synaptic Delay

Chemical synapses introduce a delay (0.3–5 ms), mainly due to Ca2+ entry and vesicle fusion. This delay is the rate-limiting step in neural processing.

Postsynaptic Potentials: EPSPs and IPSPs

Postsynaptic potentials are graded changes in membrane potential:

• Excitatory postsynaptic potential (EPSP): Depolarizes membrane, moving toward threshold.

• Inhibitory postsynaptic potential (IPSP): Hyperpolarizes membrane, moving away from threshold.

Mechanisms of EPSP and IPSP

Glutamate: Main Excitatory Neurotransmitter

Glutamate binds ligand-gated cation channels, allowing Na+ influx and K+ efflux. The net effect is depolarization (EPSP).

GABA and Glycine: Main Inhibitory Neurotransmitters

GABA (brain) and glycine (spinal cord) open K+ or Cl- channels, causing hyperpolarization (IPSP).

Synaptic Integration: Summation

Neurons integrate multiple inputs through summation:

• Temporal summation: One input fires rapidly; EPSPs stack in time.

• Spatial summation: Multiple inputs fire together; EPSPs add across space.

• EPSPs and IPSPs add algebraically; inhibition can cancel excitation.

Axon Initial Segment: The Decision Point

The axon initial segment has the lowest threshold due to the highest density of voltage-gated Na+ channels. Graded potentials decay with distance, so synapses closer to the initial segment have more influence.

Neurotransmitters: The Chemical Vocabulary of the Nervous System

Classification by Chemical Structure

Neurotransmitters are grouped into six families:

• Acetylcholine (ACh): Neuromuscular junctions, autonomic nervous system, attention, memory.

• Biogenic amines: Dopamine, norepinephrine, epinephrine, serotonin, histamine.

• Amino acids: Glutamate (excitatory), GABA & glycine (inhibitory).

• Peptides: Substance P (pain), endorphins, enkephalins (natural opiates).

• Purines: ATP, adenosine.

• Gases & lipids: Nitric oxide, CO, H2S, endocannabinoids.

Classification by Function

• Effect: Excitatory or inhibitory depends on the receptor, not the molecule.

• Action:

  • Direct (ionotropic): Receptor is an ion channel; fast, brief.

  • Indirect (metabotropic): G protein–coupled receptor; slower, broader, longer-lasting.

Drugs, Toxins, and the Chemical Synapse

• Agonist: Binds and activates the receptor.

• Antagonist: Binds and blocks the receptor.

Neural Circuits: Patterns of Synaptic Connection

Four Types of Neural Circuits

• Diverging: One neuron amplifies and spreads the signal to many.

• Converging: Many neurons concentrate the signal to one.

• Reverberating: Feedback loop for rhythmic, sustained output.

• Parallel after-discharge: Parallel paths reconverge for a burst of output.

Nerve Meets Muscle: The Neuromuscular Junction (NMJ)

Anatomy of the NMJ

The NMJ is the synapse between a motor neuron and a skeletal muscle fiber. Each muscle fiber has one NMJ, located about midway along its length.

• Axon terminals: Contain synaptic vesicles with acetylcholine (ACh).

• Synaptic cleft: Filled with basal lamina.

• Motor end plate: Highly folded sarcolemma rich in nicotinic ACh receptors (nAChRs).

Role of Nicotinic ACh Receptors

nAChRs are ligand-gated cation channels. When ACh binds, Na+ enters and K+ exits, creating an end plate potential (EPP) that triggers a muscle action potential.

Events at the NMJ: Six Steps to a Muscle Action Potential

1. AP arrives at axon terminal of motor neuron.

2. Voltage-gated Ca2+ channels open; Ca2+ enters.

3. Ca2+ causes ACh release by exocytosis.

4. ACh diffuses across cleft and binds ACh receptors on sarcolemma.

5. Ligand-gated channels open; Na+ and K+ pass, creating EPP.

6. ACh broken down by acetylcholinesterase and diffuses away.

Clinical Connections: NMJ Disorders

• Botulinum toxin: Blocks ACh release, causing flaccid paralysis.

• Curare: Blocks nicotinic receptors, causing paralysis.

• Myasthenia gravis: Antibodies destroy ACh receptors, causing muscle weakness.

• Nerve agents (e.g., sarin): Inhibit acetylcholinesterase, preventing muscle relaxation.

Grading the Force: Motor Units, Twitches, and Summation

The Motor Unit

A motor unit consists of one motor neuron and all the muscle fibers it innervates. All fibers in a unit contract together, and units are scattered throughout the muscle.

The Muscle Twitch

A muscle twitch is a single contraction in response to a single stimulus, consisting of three phases:

• Latent period: E-C coupling; no tension.

• Contraction: Cross-bridge cycling; tension peaks.

• Relaxation: Ca2+ reuptake; tension falls.

Temporal Summation: Frequency

Increasing stimulus frequency leads to summation:

• Single twitch: Full relaxation between stimuli.

• Wave summation: Stimulus before relaxation; tension adds.

• Unfused tetanus: High frequency; quivering contraction.

• Fused tetanus: Very high frequency; smooth, maximal contraction.

Spatial Summation: Recruitment

Recruitment activates more motor units, increasing force. Small units are recruited first for fine control; large units are added for power.

Isotonic vs Isometric Contractions

• Isotonic: Muscle changes length (concentric: shortens; eccentric: lengthens).

• Isometric: Muscle length stays the same; tension builds but does not exceed the load.

Muscle Fibre Types, Metabolism, and Fatigue

Three Ways to Make ATP

• Creatine phosphate: CP + ADP → creatine + ATP; lasts ~15 s.

• Anaerobic glycolysis: Glucose → pyruvic acid → lactic acid; 2 ATP/glucose; lasts ~30–40 s.

• Aerobic respiration: Mitochondria; ~32 ATP/glucose; requires O2; lasts hours.

Muscle Fibre Types

• Slow oxidative: Endurance, fatigue-resistant.

• Fast oxidative-glycolytic: Intermediate speed and fatigue resistance.

• Fast glycolytic: Fast, powerful, fatigues quickly.

Fibre Types in Real Life

Most muscles are a mix of fiber types, with proportions largely determined by genetics. Training can shift fiber properties.

Smooth Muscle: Structure and Function

Location and Layers

Smooth muscle is found in the walls of hollow organs (digestive, urinary, reproductive tracts, airways, blood vessels). Usually two layers: longitudinal and circular.

Microscopic Anatomy

• No sarcomeres; filaments run diagonally.

• Dense bodies anchor thin filaments.

• Works over a wide range of lengths.

Innervation and Response

• Innervated by autonomic nervous system via varicosities and diffuse junctions.

• Response depends on receptor type, hormones, local chemicals, and stretch.

Excitation–Contraction Coupling

1. Ca2+ enters from ECF and SR.

2. Ca2+ binds calmodulin (no troponin).

3. Ca2+-calmodulin activates myosin light chain kinase (MLCK).

4. MLCK phosphorylates myosin, enabling contraction.

Unitary vs Multiunit Smooth Muscle

• Unitary (visceral): Most hollow organs; gap junctions; contract as a unit.

• Multiunit: Large airways, arteries, arrector pili, iris; independent fibers, own nerve supply.

Special Features of Smooth Muscle Contraction

• Slow and sustained contraction.

• Economical energy use; rarely fatigues.

• Stress-relaxation: adapts to stretch.

• Hyperplasia: cells can divide (e.g., uterus in pregnancy).

Comparison: Skeletal vs Smooth Muscle

Summary of Key Concepts

1. Ca2+ triggers neurotransmitter release; receptor type determines effect; signal ends by reuptake, breakdown, or diffusion.

2. EPSPs and IPSPs sum in time and space; the axon initial segment decides whether to fire.

3. Six neurotransmitter families; effects depend on receptor and action (direct/indirect).

4. Four neural circuit types: diverging, converging, reverberating, parallel after-discharge.

5. Muscle force graded by frequency (tetanus) and recruitment; isotonic vs isometric contractions.

6. Muscle fiber types match metabolism to function; smooth muscle trades speed for economy.