BIOL 2040 – Cell Physiology & Excitable Cells Study Notes

Cell Theory and the Concept of the Cell

The lecture begins with a reaffirmation of classical Cell Theory. Cells are described as the smallest living units capable of carrying out every vital physiological process. All cells arise from the division of pre-existing cells, and the continuity of life ensures that cells across organisms share fundamental structural and functional similarities. An organism’s overall structure and performance therefore depend on both the individual capabilities of its cells and their coordinated collective behaviour.

Differentiation and Tissue Formation

Fertilisation produces a single totipotent zygote that divides repeatedly. Through the process of differentiation, unspecialised stem cells acquire specific structures, proteins, and behaviours. Ultimately, four primary tissue types emerge—epithelial, connective, muscle, and neural—each with characteristic cell morphologies and functions that trace back to gene-expression patterns established during maturation.

Universal Structural Plan of a Cell

Although ~200 human cell types exist, most share a common anatomical plan consisting of a plasma membrane, a nucleus, and cytoplasm populated by organelles. A posted organelle overview (see supplementary PowerPoint) enumerates the salient features and functions of mitochondria, ER, Golgi, lysosomes, peroxisomes, ribosomes, cytoskeletal elements, and inclusions.

Overview of Cellular Metabolism

Intermediary (cellular) metabolism encompasses intracellular degradative, synthetic, and transformative reactions. Anabolism builds complex macromolecules and tissues; catabolism breaks down large molecules, liberating energy. The immediate energy currency is adenosine triphosphate, produced primarily by three linked pathways:

  1. Creatine-phosphate (substrate-level phosphorylation) used for very rapid energy buffering in excitable tissues, e.g., skeletal muscle: \text{CP} + \text{ADP} \xrightarrow{\text{creatine kinase}} \text{creatine} + \text{ATP}

  2. Glycolysis (10 cytosolic reactions, anaerobic): one glucose → two pyruvic acids, two NADH, two ATP.

  3. Aerobic mitochondrial stages:
    • Citric Acid/Krebs/TCA cycle: each acetyl-CoA yields 1\,\text{ATP}, 3\,\text{NADH}, 1\,\text{FADH}2 and 2\,\text{CO}2.
    • Electron Transport Chain and chemiosmosis: electrons from NADH/FADH₂ ultimately reduce \text{O}_2 to water, driving oxidative phosphorylation. The exact ATP tally varies by shuttle but is often summarised as 32\text{–}38\,\text{ATP per glucose}.

Plasma Membrane Architecture

The plasma membrane is a flexible, selectively permeable phospholipid bilayer studded with proteins and cholesterol. Phospholipids are amphipathic, arranging hydrophilic phosphate "heads" outward and hydrophobic fatty-acid "tails" inward. Cholesterol modulates membrane stability and fluidity, yielding the classic "fluid mosaic model." Carbohydrate additions form glycolipids and glycoproteins that project exclusively into the extracellular space, functioning in self-recognition and cell–cell adhesion.

Membrane Proteins

Integral and peripheral membrane proteins fulfil diverse roles: receptors for chemical messengers, membrane-bound enzymes, pores or gated channels, carrier molecules, cell-identity markers, and adhesion molecules. Membrane carbohydrates (cell coat/glycocalyx) facilitate sorting of embryonic tissues, restrict overgrowth, and are frequently altered in malignant transformation.

Cell–Cell Adhesion Mechanisms

Cells are held together via (1) cell-adhesion molecules (CAMs), (2) the extracellular matrix (collagen, elastin, fibronectin embedded in interstitial fluid), and (3) specialised junctions—desmosomes for mechanical coupling, tight junctions for impermeable seals (e.g., intestinal epithelium), and gap junctions for direct ionic/metabolic communication (e.g., cardiac muscle).

Membrane Transport Fundamentals

Plasma membranes are selectively permeable. Permeability depends largely on lipid solubility and particle size. Transport modalities fall into passive (no ATP) and active (ATP-dependent) categories.

Passive Processes

• Simple diffusion moves solutes down their concentration gradients; rate is influenced by temperature, molecular weight, gradient steepness, and distance.
• Facilitated diffusion employs carrier proteins or channels for polar/charged solutes (e.g., glucose). Transport rate plateaus at a transport maximum T_m when carriers saturate.
• Osmosis is net water diffusion through aquaporins or temporary lipid gaps, driven by solute gradients. Clinical relevance appears in IV therapy: isotonic solutions maintain cell volume, hypertonic solutions cause crenation, and hypotonic solutions risk hemolysis.

Active Processes

• Primary active transport directly hydrolyses ATP (e.g., Na⁺–K⁺ ATPase exchanging 3\,\text{Na}^+ out / 2\,\text{K}^+ in).
• Secondary active transport harnesses stored electrochemical gradients (usually Na⁺) to cotransport solutes (symport) or counter-transport (antiport) others, e.g., Na⁺-glucose symport in intestinal epithelium.
• Vesicular (bulk) transport moves large particles or volumes via membrane-bound vesicles. Endocytosis includes phagocytosis, pinocytosis, and highly specific receptor-mediated uptake. Exocytosis releases secretory products or inserts new membrane components. Transcytosis combines the two to ferry material across cellular barriers.

Electrical Properties of Membranes

All cells exhibit a resting membrane potential (RMP) due to unequal charge separation. Excitable cells (neurons, muscle) typically rest near -70\,\text{mV}. The Na⁺–K⁺ pump, differential K⁺ leak, and impermeant anions generate this potential. If only K⁺ moved, the equilibrium potential would reach E{K} \approx -90\,\text{mV}; if only Na⁺ moved, E{Na} \approx +60\,\text{mV}.

Graded Potentials (GPs)

Local, decremental voltage changes result from mechanically or chemically gated channel activity. Amplitude correlates with stimulus strength and can summate temporally or spatially. Because they fade with distance, GPs serve primarily as short-range signals, e.g., postsynaptic potentials.

Action Potentials (APs)

An AP is an all-or-none, non-decremental electrical impulse initiated when depolarisation reaches threshold (≈ -55\,\text{mV}). Sequence:

  1. Rapid Na⁺ influx (activation gate opens) → upstroke to ≈ +30\,\text{mV}.

  2. Na⁺ inactivation gate closes; voltage-gated K⁺ channels open → repolarisation.

  3. Transient hyperpolarisation to ≈ -90\,\text{mV} due to continued K⁺ outflow.

  4. Resting state restored by K⁺ channel closure and continued Na⁺–K⁺ pumping.
    Absolute and relative refractory periods ensure unidirectional propagation and set maximal firing frequency.

Conduction Velocity Factors

Speed increases with axon diameter, myelination (saltatory conduction across nodes of Ranvier), and temperature. Myelinated fibres conduct up to ~50× faster than unmyelinated ones.

Neuronal Anatomy and Physiology

A typical neuron comprises a soma (cell body) with Nissl substance and neurofibrils, dendrites (input zone), an axon hillock (trigger zone with the lowest threshold), a conducting axon (± collateral branches), and axon terminals housing neurotransmitter-filled synaptic vesicles. Neuroglia form myelin (Schwann cells PNS, oligodendrocytes CNS) and contribute to support, immune defence, and homeostasis.

Synaptic Transmission

An arriving AP depolarises the presynaptic terminal, opens voltage-gated Ca²⁺ channels, and triggers vesicular exocytosis. Neurotransmitter diffuses across the synaptic cleft (≈ 30–50 nm) and binds postsynaptic receptors, opening ion channels.

Excitatory vs Inhibitory Synapses

• Excitatory postsynaptic potential (EPSP): usually Na⁺ or Ca²⁺ influx → depolarisation.
• Inhibitory postsynaptic potential (IPSP): often Cl⁻ influx or K⁺ efflux → hyperpolarisation.
The grand postsynaptic potential (GPSP) is the algebraic sum of all concurrent EPSPs and IPSPs. Integration follows temporal and spatial summation rules; action potentials are triggered at the axon hillock if GPSP reaches threshold.

Neurotransmitter Dynamics

~100 identified transmitters range from single amino acids (glutamate, GABA, glycine) to biogenic amines (dopamine, norepinephrine, serotonin) and acetylcholine. Each presynaptic bouton generally releases a single classical transmitter whose action is terminated by diffusion, enzymatic degradation (e.g., ACh‐esterase), or reuptake (e.g., dopamine transporter; cocaine blocks this, prolonging dopaminergic signalling).

Neuropeptides and Neuromodulation

Larger 2–40 amino-acid peptides (substance P, endorphins) are synthesised in the soma, packaged in dense-core vesicles, and released with lower frequency. They seldom open ion channels directly; instead they modulate synaptic efficacy over longer timescales by altering receptor or enzyme populations.

Presynaptic Modulation

A third neuron can synapse onto the axon terminal of another (axo-axonic synapse) to inhibit (presynaptic inhibition) or enhance (presynaptic facilitation) transmitter release, providing fine control over synaptic strength.

Convergence and Divergence

Neural circuits exhibit convergence (many inputs onto one neuron) and divergence (one neuron influencing many others), enabling complex integration and widespread distribution of information.

Degeneration and Regeneration

In the PNS, Schwann cells form regeneration tubes that permit slow (≈1 mm/day) axonal regrowth if the soma remains intact. CNS axons generally fail to regenerate because of inhibitory proteins from oligodendrocytes and rapid scar formation.

Clinical and Pharmacological Correlates

• Tetanus toxin blocks release of inhibitory GABA, causing uncontrolled muscle spasms.
• Local anaesthetics block voltage-gated Na⁺ channels, preventing AP initiation.
• Certain disorders (multiple sclerosis) involve demyelination, slowing saltatory conduction.

Self-Assessment and Review

Embedded slides provide multiple-choice questions covering extracellular terminology, membrane composition, diffusion/osmosis concepts, transport modes, neuroglial functions, action-potential phases, and synaptic mechanics. Students are encouraged to attempt textbook problems (Chapter 2 & 3) and consult linked Crash-Course videos for reinforcement.