Excitable Tissue

Physiology

• Physiology is the study of the normal functions in a living system, including cells, tissues, organs, and the body as a whole
• Human physiology specifically studies the normal functions occurring in the human body
• The Royal Swedish Academy of Sciences awards the Nobel Prize in Physiology or Medicine for outstanding scientific achievements in physiology related to medicine

Key Topics in Physiology

• Physiology of excitable tissues is covered in lectures and seminars
• General physiology is covered in lectures and seminars
• Physiology of blood and immunity is covered in lectures, seminars, and online learning materials
• Physiology of the central nervous system (CNS) is covered in lectures
• Physiology of special senses is covered in lectures
• Physiology of endocrine glands is covered in lectures
• Physiology of reproduction is covered in lectures
• Cardiovascular physiology is covered in lectures
• Physiology of respiration is covered in lectures, seminars, and a textbook
• Renal physiology is covered in lectures
• Physiology of the gastrointestinal tract is covered in seminars and a textbook

Practical Classes Schedule (Winter Semester 2024/2025)

• October 1 - October 25, 2024: Physiology of Excitable Tissues and General Physiology, with a credit test (4 weeks)
• October 29 - November 22, 2024: Physiology of Blood and Immune system, with a credit test (4 weeks)
• November 25 - December 13, 2024: Physiology of the Nervous System and Special Senses, with a credit test in Physiology of Special Senses (3 weeks)
• December 16, 2024 - January 10, 2025: Reserve time for substitute exercises and credits

Physiology of Excitable Tissues

• Cell membrane structure and function is essential in understanding excitable tissues
• Membrane channels are key for ion transport
• Membrane transport mechanisms facilitate movement of substances across the membrane
• Resting membrane potential determines the excitability of the cell
• Graded potential and its propagation are important for signal transduction
• Action potential and its propagation enable rapid communication over long distances
• Neuromuscular transmission is the mechanism by which nerve cells communicate with muscle cells
• Skeletal muscle physiology focuses on the function of voluntary muscles
• Cardiac muscle physiology focuses on the function of the heart muscle
• Smooth muscle physiology focuses on the function of involuntary muscles

General Physiology

• Cell structure influences overall body function
• Homeostasis regulates balance in the body
• Fluid distribution within the body is important
• Intercellular communication is important for coordination
• A synapse transmits signals between cells
• Membrane receptors recognise specific molecules

Functional Morphology of the Cell

• The cell membrane's structure enables multiple principal functions
• The nucleus and nucleolus have a specific composition and function
• Ribosomes are related to the endoplasmic reticulum, both playing a key role
• The endoplasmic reticulum facilitates intermediary metabolism and calcium ion storage
• The Golgi apparatus is an organelle within cells
• The cytoskeleton is composed of fiber types that enable key cellular roles
• Mitochondria are structured for intermediary metabolism and energy production
• Lysosomes and peroxisomes in cells function to recycle components

Biological Membranes

• The cytoplasmic membrane in cells consists of phospholipids, with importance in structure and function
• Membrane fluidity can be affected by several factors
• Integral and peripheral proteins in membranes enable function and stability
• Glycocalyx is a surface structure on many cells

Membrane Channels

• Channels are Classified by selectivity, localisation, and gating
• Voltage-gated membrane channels are diverse in function and examples
• Ligand-gated membrane channels work through typical ligands and examples
• Mechanosensitive membrane channels have unique localisation and function
• Intercellular channels facilitate direct communication between cells

Membrane Transport

• Extracellular and intracellular fluids have different compositions
• Active and passive transmembrane trafficking moves substances
• Fick's first law of diffusion dictates passive diffusion
• Active transport needs primary and secondary mechanisms and examples
• The mechanisms of symport and antiport enable transport
• Endocytosis and exocytosis enable bulk and selective uptake/release

Excitable Tissues Definition

• Excitable tissues are capable of generating and transmitting electrochemical impulses in the form of action potentials along their membranes
• This capability is determined by the structure and function of the cell membrane
• The excitable membrane in neurons covers the axons
• Muscle tissues are excitable: skeletal, cardiac, and smooth

Cytoplasmic Membrane

• A semipermeable barrier made of lipids and proteins
• Selectively controls the passage of molecules between the cell interior (ICF) and the extracellular fluid (ECF)
• Lipids in the membrane consist of Phospholipids, Cholesterol, and Derivatives of sphingosine
• Proteins in the membrane consist of Integral and Peripheral types

Factors Affecting Membrane Fluidity

• The proportion of unsaturated fatty acids
• The ratio of cholesterol/phospholipids
• Physical and chemical factors
• Certain compounds like ethanol and anesthetics

Membrane Proteins

• Typically make up about 50% of the material in the membrane
• Integral proteins completely span the membrane or are embedded without fully crossing it
• One or more transmembrane domains are permanently attached to the membrane
• Integral proteins are separable using detergents or denaturing agents
• Peripheral proteins are non-covalently bonded to integral proteins or the lipid bilayer via hydrophobic bonds
• Polar reagents can dissociate peripheral proteins from the membrane

Transport Proteins

• Channels passively allow specific molecules through membranes
• Transporters change conformation to carry compounds across membranes

Structural Proteins

• Anchoring proteins
• Adhesion molecules

Cell Communication Proteins

• Receptors bind and start signals
• Antigens

Enzyme Proteins

• Oxidoreductases
• Transferases
• Hydrolases

Glycocalyx

• A glycoprotein-polysaccharide coat on the exterior of plasma membranes that has oligosaccharides, glycolipids, and transmembrane glycoproteins
• Functions include cell recognition, cell adhesion, intercellular communication, and protection/permeability

Cell Membrane Functions

• Creates a selective barrier between the ICF and ECF, controlling the ions and proteins that enter or leave the cell freely
• Structural roles maintain cell structure
• Protective traits from external chemicals
• Communication through receptor sites
• Metabolic processes through selective enzymes

Membrane Channels Overview

• Composed of several subunits and many transmembrane domains
• Represents a water passage through the membrane
• Selective for a distinct ion
• Classified according to: Presence of Gates, Selectivity and Localization

Membrane Channels Classification According to the Presence of Gates

• Gated channels
• Non-gated background channels eg IK1

Membrane Channels Classification According to Selectivity

• Calcium Ca2+
• Potassium K+
• Sodium Na+
• Chloride Cl-
• Water H2O

Membrane Channels Classification According to Localization

• Cell membrane channels
• Endoplasmic Reticulum Channels
• Mitochondrial Channels
• Vesicular Channels

Gated Membrane Channels Classification

• Voltage-gated channels are activated by changes in membrane potential
• In voltage gated channels, INa, IK, ICaL cause action potential
• Ligand-gated channels (N receptor of neuromuscular junction) and require a specific molecule to bind and open
• Mechanosensitive channels are activated by physical stimuli, such as pressure or stretch (proprioception, hearing)
• Other channels can be gated by factors such as temperature, electromagnetic waves, and water (aquaporins)

Voltage-Gated Channels regulation

• opening and closing are regulated by membrane voltage
• Minimum potential change needed for opening is the threshold

Ligand-Gated Channels Opening

• Caused by a chemical messenger attaching to chanel protein
• Channel events depolarize/hyperpolarize the cell membrane.

Active Transport: Composition of Intra- and Extracellular Fluids

• Sodium Na+ : ECF is 145 mmol/l while in the ICF is 10 mmol/l
• Potassium K+ : ECF is 4 mmol/l while in the ICF is 140 mmol/l
• Calcium Ca2+ : ECF is 1.2 mmol/l while in the ICF is 10-4 mmol/l
• Magnesium Mg2+: ECF is 0.5 mmol/l while in the ICF is 1 mmol/l
• Chlorhide C1-: ECF is 100 mmol/l while in the ICF is 5 mmol/l
• Bicarbonate HCO3-: ECF is 25 mmol/l while in the ICF is 10 mmol/l
• Protein A-: ECF is cca 4.6 20 g/l while in the ICF is cca 35 160 g/l

Fick's First Law of Diffusion

• Important for gases (O2 a CO2), compounds soluble in fats, nutrients, waste products; partly for water and electrolytes
• Is expressed as J = -D. grad (c) and J = n/A.t (mol.m-2.s-1)
• J = -D. Δc/Δx
• J diffusion flux in mol/m²/s, D diffusion coefficient in m²/s, grad (c) concentration gradient in mol/m², A diffusion area in m², Дс concentration difference in mol/m³, Ax diffusion distance in m.

Key Equations of Diffusion

• J = -D . grad (conc))
• J = -D. Ac/∆x mol.m-2.s-1
• J = n/S.t

Facilitated DIffusion

• 1 substance (uniport)
• The by conformational change of protein carriers (transporters) after binding of the substance
• Occurs in glucose (GLUT), amino acids, epithelial membranes in the gut and renal tubules

Facilitated Diffusion in comparison to simple diffusion:

• Transport maximum/ Vmax
• Diffusion flux increases proportionally to the concentration gradient in simple diffusion
• Diffusion flux in facilitated diffusion has certain maximum value/ Vmax - determined by maximum velocity of conformational changes in transporter molecule

Types of Transporters

• H-ATPase, NA-K, cotransporters: glc, Na+, Ca2

Active Transport (Primary): Composition

• It goes against electrochemical gradient
• Consumes energy (ATP)
• Needs protein transporter that has its own ATPase activity
• In Na+/K+-ATPase, 3 Na+ are moved out in exchange for 2 K+ inside per 1 ATP molecule consumed
• Electrogenic, maintenance of different Na+ a K+ concentrations out of and inside the cell

Active Trasport (Secondary or Cotransport)

• The types of secondary transport involve 2 separate transported compounds: SGLT, NCX etc.; 3 compound eg Na-K-CI transporter in thick portion
• Symport involves cotransport of glc and Na by luminal membrane
• Antiport works as NA/ Ca exchanger in sarcolemma of cardiomyocytes

Endocytosis Overview

• Phagocytosis: engulfing of big solid particles (aggregates of macromolecules), antigenically altered cells, foreign microorganisms
• Pinocytosis: internalization of ECF including dissolved substances as well as ATP consumption
• Receptor mediated occurs when LDL, transferring, IgG from mother, insulin, growth factor, etc bind to membrane receptors

Steps of Receptor-Mediated Endocytosis

• After a ligand binds the membrane receptors, the receptors start to accumulate in one spot of the membrane by a clathrin coated pit
• Proteins such as clathrin and adaptin are part of the vesicle
• The mature pit will form a vesicle that breaks off the cell
• The new clathrin-coated vesicle will move to an new endosome

Exocytosis

• Secretory vesicles move/attract to a different location
• Two membranes bind > a release
• There is frequently an increased presence of Ca2+ concentration
• Exocytosis has energy consumption traits

Transmembrane Dynamics

• Coated vesicles travel with cell along microtubules toward a destination
• Prior to docking the previous vesicle, the old cell loses its own coat and reveals a class of SNARE molecules

SNARE molecule overview

• SNAREs: v-SNARES (vesicle membrane) and t-SNAREs (target membrane).
• The v-SNARE and t-SNARE of membranes touch each other and combine to form a coil. This enables the membranes to shut close in contact.
• SNAP can attach to proteins and enable fusion.
• NSF is another protein that is a sensitive factor.