Cell Physiology: Neurons and Muscle Cells

Topic 1 - Cell Physiology

• Four broad cell categories exist: neurons, muscle, epithelia, and connective tissue/support cells.

Neurons

• Neurons facilitate cell-cell communication through electrical and chemical signals, controlling the body's responses to internal and external changes
• They are located in the brain, spinal cord, and peripheral and autonomic nervous systems
• Neurons feature dendrites that receive and integrate signals, stemming from the cell body/soma, where signals are generated
• These signals are propagated along a long axon to a receiving cell at the terminal leading to chemical communication
• These electrical impulses are action potentials, which are transient shifts in the neuron's membrane potential caused by ion flow

Muscle Cells

• Muscle cells contract, generating force and movement, both voluntary and involuntary
• They are present in skeletal muscles, heart, viscera (organs), and vessels, and include subtypes connected end to end or side to side
• Smooth muscle facilitates peristalsis in the digestive system
• Skeletal muscle attaches to bones for movement
• Cardiac muscle is specific to the heart

Epithelial Cells

• Epithelial cells transport substances between extracellular compartments, secrete/absorb substances, and maintain homeostasis
• They occur in single or multilayered sheets, each cell having two polarized/specialized transport sides
• They are in exocrine and endocrine glands (e.g., pancreas, sweat glands), secreting and absorbing organs (e.g., kidney), and organ linings
• These cells line internal organs exposed to the external environment to regulate what enters the body, and also line blood vessels to regulate blood contents

Connective Tissue and Support Cells

• This group includes non-cellular fibrous and elastic connective tissues, lipid storage, and mobile cells protecting the body
• Examples are fibroblasts (secrete/regulate collagen), bone cells, fat cells, blood cells, and macrophages
• Microglia, macrophages in the brain, consume cell debris (phagocytose) and form scars around damaged areas for recovery

Cells - Common Features

• Cells consist of 60-80% water, optimally 70%, with proteins making up almost half of dry weight, followed by nucleotides (~30%) and lipids
• They also have sugars, amino acids, and hydrated ions
• Cell diameters vary from 1~100µm, with volumes from 1-500kµm³
• Total body water (TBW) in average males is 42L, with intracellular fluid (ICF) at 28L, and extracellular fluid (ECF) at 14L
• Plasma fluid constitutes 3L, and interstitial fluid (ISF) constitutes 11L, sharing similar compositions to plasma
• ICF is high in potassium but low in sodium and chlorine, whereas ECF is rich in sodium, chlorine, and calcium ions
• The cell membrane, a lipid bilayer with embedded membrane proteins, mediates cell-cell communication and acts as a barrier between ECF and ICF
• Thin (10-20nm thick), it encapsulates the cell and manages transport in, out, and across
• Lipids and proteins flow within the fluid mosaic model of the plasma membrane
• Membrane lipids feature hydrophobic hydrocarbon tails and polar (hydrophilic) headgroups
• Tails connect to, and headgroups face, the solution, thus the lipid bilayer makes the membrane impermeable to water and water-dissolved substances, separating external and internal fluids
• The many membrane proteins include integral (spanning lipid bilayer, e.g. 1-2), lipid-anchored (attaching to bilayer, e.g. 3-4), and peripheral (adhering temporarily, e.g. 5-6) types
• Single cell membranes have millions of proteins, including transporters, cell signaling receptors, and adhesion molecules to connect/link cells

Membrane Transport - Passive Membrane Transport

• Passive membrane transport involves diffusion of substances down an energy gradient
• Diffusion is passive movement from high to low concentrations due to random molecular motion of atoms and molecules
• Fick's Law measures this movement as J = DA (dC/dx), where J is flux (Mol/cm²/s), A is area of interface, dC/dx is solute concentration difference, and D is the diffusion coefficient (cm²/s)
• The diffusion coefficient changes for different molecules and is related to the speed of the molecule's random motion
• For membrane diffusion, K (partition co-efficient) must be introduced, with J = KDA (dC/dx)
• Lipid-soluble or hydrophobic substances (e.g., gases, steroids, hydrophobic drugs) pass through simple diffusion
• Water-soluble/hydrophilic substances (e.g., ions, glucose, amino acids) with small K pass with facilitated diffusion via a transporter protein
• Recent updates to Fick's Law include transport proteins as J = PA (dC/dx) = PAA C, where P = Permeability (cm/s)
• Permeability depends on quantity and speed of protein transporters
• K+ ions easily cross cell membranes due to rich K+ transporters, thus K+ is a permeant ion
• As absolute permeability is hard to measure, relative permeability is often used, measuring against K+ and Na+
• Different protein transporters have specificity to certain substances
• Drugs can compete by blocking the entry of intended substances with a more efficacious structure
• Facilitated diffusion flux is limited by saturation where carrier sites are occupied despite solutes remaining unlike simple diffusion

Membrane Transport - Active Membrane Transport

• Active transport requires that energy move substances up against their energy gradient
• Primary active transport directly spends an energy source to move a substance gradient
• In mammalian cells, ATP powers ATPase pumps
• Na+ pumps are ubiquitous, maintaining Na+ and K+ gradients between ICF and ECF
• These gradients provide energy for secondary transport and electrical signaling, which are crucial for cell functions
• Seconday Transport indirectly uses energy sources to move things against a gradient
• In mammals, Na+ or K+ gradients are the typical energy source
• Sources come as co-transporters (solute traveling down its gradient pulls another against), or counter-transporters (a solute traveling down its gradient drives another against)
• Secondary active transport transports ions, sugars, amino acids, neurotransmitters etc

Membrane Transport - Endocytosis and Exocytosis

• Endocytosis and exocytosis involve incorporating substances into a lipid bilayer vesicle, which fuses with plasma membrane to release contents to ECF in exocytosis, or forms from the plasma membrane to capture extracellular contents through endocytosis
• An example of exocytosis is hormone release from endocrine glands into the bloodstream
• During nerve terminal exocytosis, neurotransmitters package into vesicles transported to and docked to presynaptic membrane and primed for release
• Activated by Ca2+, specific pathways and proteins cause the vesicles to fuse to the plasma membrane to release their contents into the synaptic cleft
• During nerve terminal endocytosis, vesicle lipids that fused to the membrane are tagged and reformed into a new vesicle separating and repackaging the neurotransmitter

Endocytosis Subtypes

• Phagocytosis: used by macrophages to engulf cellular debris, bacteria, and food
• Pinocytosis: liquid is engulfed and brought into the cell
• Receptor-mediated endocytosis: specific molecules e.g. low-density lipoproteins (LDL) bind to receptors and trigger engulfment

Transporters and Osmosis - Molecular Physiology of Transporters

• There are 14 different "Glut" facilitated glucose transporters, most commonly Glut1 (known as "occluded access" and carrier-mediated)
• Glucose binds to the binding site on the ECF side, trapping itself and causing specific conformational changes
• These conformational changes release the trapped glucose within the ICF
• Glucose is also transported by secondary active Na+-dependent transporters
• 2 Na+ bind to the ECF side which allows glucose to bind in order to facilitate a conformational change that flips the transporter, releasing the glucose and Na+ to the start the bare transporter
• SGLT1 (sodium glucose transporter) - in intestine, glucose absorbs from bloodstream
• SGLT2 - in kidneys, glucose re-absorbs from blood
• Ion channels are a diverse family of facilitated transporters. The transport is determined by ion movement "downhill" through a central aqueous pore that spans the membrane
• Different channels select for specific ions to various degrees(selectivity), and channels may be always open (pores) or gated (closed and open conformations)
• Ions generate a change in ICF voltage w.r.t ECF voltage (basis of electrical signaling)
• Ion channels are gated through four main modes:
• Binding of an extracellular ligand (e.g. neurotransmitter activated channel)
• Intracellular phosphorylation or binding of an intracellular ligand (e.g. a cellular messenger activated channel
• A change in the membrane potential (e.g. a change in membrane potential opens or closes the channel)
• "Background","Leak" channels or "Pores"
• Stretch of the membrane

Transporters and Osmosis - Osmosis

• Osmosis diffusion of water down a water concentration gradient, occurs through simple diffusion and facilitated diffusion
• Water has a higher molar concentration than solutions with solutes dissolved in them, water has a lower concentration.
• Osmolarity is the concentration of solute particles per litre
• Aquaporins are integral membrane proteins aiding water transfer across the membrane, containing a pore at the centre of each aquaporin molecule

Membrane Potentials - Electrochemical Forces

• Body cells are polarized and have different voltages inside compared to outside
• At rest, nerve and muscle cells are about 0.1V more negative on their inside surface compared to outside
• Membrane potentials are caused by ions flowing across cell membranes, membrane must be permeable w/ channel
• Ions enabled if diffusion gradient or an electrochemical energy is present
• Like charges repulse, opposite charges attract, cation attracted to negatively charged inner, anion drawn out to their outer
• When chemical and electrical force is balanced there is electrochemical equilibrium Equilibrium/Nernst Potential given as: Vm=(RT/zF) ln ([X]₀/[X]ᵢ) or at 37C Ex≈62mV log([X]₀/[X]ᵢ) -If the membrane is permeable to an ion, it will keep flowing to keep conditions equal

Membrane Potentials - Membrane Potentials

• If only one ion is permeable, the membrane potential will be equal to the amount of the ion
• If both exist, Vm will somewhere in between which related to permeability
• Nerve cells in an equilibrium are roughly -70mV, they are not at equilibrium but rather in flux

Action Potentials

• If we stimulate a nerve cell with a current, and exceed the threshold, failure occurs
• Reaching supra-threshold allows activation around (-40 to -50 mV).
• Typical resting membrane around (-70 to -80mV)
• Threshold is reached and opens channels up to voltage gate

Action Potentials (Molecular)

• discovered in fruit flies, now 70 humans
• brain K+ and heart K+ genes are not equivalent
• voltage sensors detect and act as molecular switches

Action Potentials(Na+ channels)

• voltage dependent with two gates, activation and inactiviation
• Inactivation swings in to stop permination
• When blocked it cannot perform a reaction called the absolute refractory, ~1-2 ms. action does not occur thereafter is the second wave where the reaction is hard, but not impossible
• can differ to generate different reactions
• in heart AP can voltage Ca2+ lasting up to 400 ms

Action Potentials(Signal Propagation)

activated nerve cells send signals using synapses, faster if myelinated:

• initiated near region "axon hillock", if not in axon the spread is small
• the spread flows from the axon to invert their charges
• passive spread with electric cable will decrease magnitude
• Active propagation sustains the function and is only for the threshold

Action Potentials(Myelination)

• unmyelated axons at 1m/s, thus occur with critical signalling
• decrease current leak + spread the depolarization
• Node to node transfer occur as AP
• up to 120 ms/s motor + sensory control are efficient
• shwann cells which wrap around axons form the myelin sheaths
• in CNN, they are oligodendrocytes

Synaptic Transmission

• Communication can be direct through ion/molecules using gap junctions
• coupled cells share an ion concentration and act together, example heart, peristalsis

Chemical communication

• release messenger with reciptor -paracrine: adj cell and adj receptor
• autocrine: secretes with target
• typically nerves + neurotransmission, presynaptic cells
• endocine: sends distant signals through the blood

Transmitters for Chemical transmission

• two classes, Metabotropic and ionotropic Metabootropic: actives intracellular sending, and G protein couple receptros, activates enzymes for Iontotropic: trigger ionic flux
• Fast respones in neurotransmitters are in specific receptros
• AP in NMJ causes voltage triggering + Calcium exocytosis of acetylcholine into gap and binds postsynaptic receptors
• Nicotinic receptors cause allow influx Na which depolarizes and the muscle creates a AP/ impulse -the muscle is recycled with esterrace Acetylcholinesterase

Synapses

• each has up to 1000 synapses, signal fire required,
• coord,depolarzization, more excitatory
• excitatory cause neuron more likely to fire, ligand channels triggers positive Na ,Glutimate
• inhibatory, less likely to have high pressure. ligand releases cloride for inhibation, GABA releasing more inhibitory activation
• brain depends relies on inhibition + excitement
• high pressure : seizure, anxiety and other
• inhibition high: sedation and analsegics
• the decription to out put = integral summation

Neural Transimtter

• repeated activation can produce large syn, resposnes when it goes above a voltage / termporal

• spatial : activation of diff syn

• can cancell eah others effect

• removed or go back using reuptake

• Drugs effect the effect of prolonging the reception enzymes can breakdown the transmitters and recyle like poison, target, cause the muscles toparalaxlise Receptors may desensitize or become innervated in the acute or chronic effect Neuotransmiters - terminate via diffusion

Topic 2 - Muscle Contraction

• activate volumantrily vs cardial and skeletal muscle
• Muscle is a big bundle( fasciles (fibre), fibre are one unit cell
• one cell has chainlike protein where each link -sarcomere

Muscles

• sarcomoeres contain myosin, thick and filaments Both have are Quartenary Muscles of mysoin double as double Heical Skelatels contain collagen

Muscle fibres

shape- elongagted, cilidnrical shape, with pattern

• Cells are nuclei, one or more at the cell
• sarcomlelmme, cells membrane, blocks pattern
• band, contanins mainin to darken
• Disc are borders where actions are attached to main
• Dircs approach eatch others where myosind moves in width
• all contanract are the same time

Skeletal Muscle

E-C: copuling the process into

• muscle action potental
• motor creates creates fire by chemical transimissino
• nuromucular connectivtion
• ach released and produce in AP

Fibres

contains T tunnel the muscle follows to connective tiisue, the conttraction is uniform

• Tunnles form through calcium chanels Sarcoosplas reticulum has more in skelealt, releases more

• Muslce AP leads to depolarization of sacromelmma, chanes the voltage

• lead to a mass of calcium and then the membrane start to consttrct

• fibres contract will still have free calcim can fromSR

Muscle(Cycle of contraction)

Calcim is released to topoinon binds

• myison binds requiruing ACTP
• it is hydrolyzed, energy released to pull myosin
• Myosin-ADP lower strength as it pulls towards
• adp releases

Muscles(Rest and force)

Fibre potentionnal lasts only a few as they try to relax the potentual

• if calcim cant be lowere it will create danage rest proect starts by calcium and protein bonding calcium pumped to as reutake
• in presecnse force of structurel
• muscles has high rate of actin

Fatiques

Unfused, incomplete contartcion, complete no redlax, bue clels will not decrease

• Tetanus cant decrease in concetrations
• alpha moner neuron contrls all muscle force
• singe ap in alphas all fibre units. diff neurons generate outputs

Contractions and Force Outputs

-the the unit increases smalls gerenarte fircs and later get motr bigger, the size conts. the intaila force detmenr of the force

• excerise to can incrase fibre sizee to prodcuue more
• larger yiled the better
• -types of contarction, constant tension while lenght will
• contriction tension while develps

Skeletal muscle

Types of Fibre fibre types differs on demands

• lowe forces that susutain contriction
• high mito and cao, to a red color
• Fast has high acvitivy low mito and appear white
• some fibres suited diff acuviies

Cardiac Muscule

• only found in heart atira, ventricles. the heart
• myocite from network and connects other
• has a central nunclou

###Cardiac(Cell Contacts)

• Gpa are tunneols which small mole can use
• tubele, tubule, has only 1 sr termina, therefore dialate
• only on continous app to reqire for

Cardiac Structure

• heart will undergo atp synthies with a aeribics procss
• conteint many more mito then others
• heart has intrincit set of pace markers callel sa node
• these cell deopaliszers , then ap atria and conatircle

Action Postential

• controls transmier noradrenaline or accetlcloline
• noreadline enhance the amploiying in pace makers , ach lower depplarzing carlac ap has is 200-300 ms with a heart beat longer then muscle cell

Properties

distincitnve calcium curerbt through cahtnnels adds phase to caprdiac action potenials

• long laisting leads refartiry longer time to muscle Continous requreire atp

• calcium relases process are intaied by tubules to atp,

DHP cahnnels casuse curretn for ytsol Calcium concentration activates Ryr calcium channles in store

• feedback mechansim

Cardiac structure

• relye on ca, buffering an active pumps cytosis bufferin calcm tranfer extrude ,,,
• has spindles cells and aotmions

-actins -proetin to zdisc

• haev cavloare

Cardiac types

can organized in groups one or multi

• singel unif gao juicition and eachother
• contarctions throughout network then creates are wavily
• mulyi dont doreclt cantract

The Muscles

General contration occurs: increased c, ionotropic ,mechanosintive.metabotropic receptors release sr through c calcium pos

Ca has faster respons , similar role thn tnc, sensor actives the light chaim gives high atp acticvitity

RELAXATION

muslce

• Dephyosporylates
• Buffed Ca, then repuptkae sends a potneial with pumpls calcium atpase

Topic 3 - Automatic Nervous System -

• Now a days the CNN and PNS are both included, Autinome control fours Fight, Flght, Feeding
• The Autinome*
• in the emotinons and physical
• and the reverse effects what is going on emotion
• leads to snesory input to automatic

automatic effects :

• effextor or entiritic in no
• signals travel of integration through
• Brain steum integration across sytsm
• CNS: desirs NUCLEI CAN : COMULATE -para rest, symathetics for flight Eniritic controls mility

Afferent nerve -system

Autinome-Details of Function

• efferent plans the PNS, and interats
• Symathetics in the THORACTIC, the parasymp in stem
• Chains of ggland the parasympathetic and is short, like brain stem
• most of recipricol
• symaticty goes thru chain/ + collateral ganglia
• Sympthetics usually use collateral

Action Potential

-pre gang interacts while is travellin Synaptic the synapse it grester, for overflow though ACH is bond ot actel choline, the muscurinic Is

System Functions

Barrow reccpetoes : after vesse;s System functerion: cardiovascular

Para System Sympathetic heart increase heartrate heart decrease heartrate Decrease -contracrt, and inverse

-digeatibe ,,, motility increase , decrease motility and increase , inhibtede creetion spinchter: increase increase the creatuin the kidney the urianrynary ballade and decrease force the procreate

Functions Nerve

• The reate is increase at the symathiec

• Epeffect : Organns- most vaculas smooth
• -CNS and adriopse tissue, cns kidney,
• -SOME BLOOD VESSELS, repiratoy tract uterus

Cardiac system - Overview

• hearts pump that drives blood throgh the rest all part s
• supples o2+remomves waste, performs sensory eendocron functy blood vessels blood presusre, carries hormones substan

###The Hearts structure

Hallow surrounded with red and with to separate pumps

• pumps the pulminay circ and to the other parts of the the systmcit pumo has upper atria recieves it , and lower ventrical to generste the forv The to atrica spearated by inatrica ventircualr sepatre prevent mixing blood from the lungs enters atria, mitral , aortic , into arota The arteris branch into arertioles into capillares and that transorts ox blood

Parts function/flow

• -aeritoles,capitallares are vollected into microciculation circuit
• -flows through the pulmonarory valve into thr pulmonarry trunk
• • immdeiatelhy branch to carry deox blood to each lunge
• -- Oxygenated is then enter thru pulmonary
• arteriolies carry ox , veins carry deox except pulm veins

Blood volume

• mean volyums, highy est sylstoalic pressure diastitic pressure pulmonary artery presure low with system , high presuure
• blood valves are one direction and open when presure changes

Ati and ventri valves are the flaps at endocarpium whjch achre

• three three flasps , bicaspedal

-semiulnaar are prottact retunring blood ventrilces for consitiction

—thickers than atrial bc ventircales must pump further

• Atrial ventalic and atrial sepereate d by trissue

The Heart

The heart containes the follwing chateistics:

• muscle fibers arranged and interacatlve
• electircal+ phsycial couplings
• contains desmosomes
• the heart as a ans and symathetic nerves
• increases by heartrate and conractions

System( Output)

The qty outout of the blood and each time by heart and beat CO is + heart rate _ V At rest the about 5L and targets abdonom

• prelodes- stress to stretch, increasing prelaod to increases prelauys increase v Starling affirms :blood to flood Ef can used to by end voume

Physiological key

-force needed to open valcs (

• afterload increases
• more conteacion

Myocardis- is change fo contraction due to or heartrate

Highy incrse cons, -Adreiline will active it and increases calcium which also increase speed

Lcal controlls of blodd:

TISSUES AND RREIUQRMNETS recreives is proprotionat to the requirmenets

• livers and kidnesy

autoreugation , to reail contsant when pressuea

Increadrs pressure caure constrtivion viceersas

More

local has high rate as it increase fuhrer

• coronay blood flows from the root, can be paunful aedoside dialtes its to c02 levels to increast

THe veins

aids in constrition

• cutanou: there

the the external enviroment, body follows thermo, which trigger cardio to increase sum. in vaskn for heat

• -muscle and active metabilitn

• then muscles , acts as a the diliaet in to relse

• Brain ,high demand on brain , complicated access fatty acis

• low pressure , prevent s water

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