cell physiology Flashcards
ion channels
ion channels are:
* Selective.
* Conductance(measured in picosiemens (pS)).
* The single-channel conductance of typical ion channels ranges from 0.1 to 100 pS.
* Gating = Fluctuation between open and closed states.
controlling ion channels:
membrane voltage (e.g. depolarisation)
extracellular agonists or antagonists (e.g. lig and gated)
intracellular messengers (e.g. Ca2+, ATP, cGMP).
mechanical stretch of the plasma membrane (physical stimulation).
Describe different types of ion channels and explain the term “channel gating”. —
ionotropic receptors
Ligand-gated ion channels made of 3, 4, or 5 protein subunits that together form an ion-conducting pore in the center of the receptor.
Activation of receptor causes a pore to open through which ions can pass.
Examples include:
- Ligand gated sodium channels (eg. AChR nicotinic not muscarinic).
- TRPV1 receptors (receptor for capsaicin found in hot chilli peppers).
Fast acting
“On” or “Off” - All or None
Receptor is made up of multiple subunits
Example of function is in triggering an action potential.
metabotropic receptors
AKA G-protein coupled receptors
Activation of receptor initiates an intracellular signalling mechanism (ions do not pass through the receptor protein).
Examples include:
– Metabotropic glutamate receptors (mGluRs).
– Adrenergic receptors of the autonomic nervous system (e.g. beta-adrenergic receptors in heart).
Slower prolonged response compared to ionotropic receptors.
Can amplify or dampen signals:
Gs = stimulatory.
Gi = inhibitory.
Receptor proteins are monomers.
membranes and movement of water
Hydrophobic core.
Effective barrier to movement of virtually all biologically important solutes.
Intracellularandextracellularfluidsareprimarilywater(in which solutes such as ions, glucose and amino acids are dissolved).
Gases(e.g.,O2 and CO2)and ethanol can diffus eacross lipid bilayers.
Movement of water and solutes is restricted.
Membranes are not very permeable to water
* Water channels = Aquaporins (AQPs) image is human AQP1.
* Widely distributed throughout the body, especially in kidney.
* Different isoforms found in different cell types.
* Amount of H2O influx/efflux can be regulated: – altering number of AQPs in the membrane
(membrane protein trafficking)
– changing their permeability (i.e. gating) e.g. by pH
Outline the general properties of carrier mediated transport systems.
solute carriers
3 major functional groups:
1. Uniporters (transport one substance).
2. Symporters (transport more than one substance in the same direction).
3. Antiporters (transport substance in different directions).
uniporters:
Transport a single molecule across membrane.
Example: GLUT2 (brings glucose into the cell).
Mutations can cause diabetes.
symporters:
Couple the movement of two or more molecules/ions across the membrane.
molecules transported in the same direction (co-transport).
Example: NKCC2 found in the kidneys
1Na+,1K+,2Cl- symporter.
critically important for diluting and concentrating urine.
antiporters:
Couple movement of two or more molecules/ions across the membrane in opposite directions
Also called “exchangers” and “counter transporters”
Example: Na-H exchanger
– Na+-H+ antiporter
– found in all cells
– important role in regulating intracellular pH
other examples of carrier mediated transport systems.
H+ -ATPase
Vacuolar H+-ATPase: found in membranes of many intracellular organelles (e.g. lysosomes)
Plasma membrane H+- ATPase: important role in urinary acidification
ATP dependant ion transporters:
Example: Na+, K+ATPase (also called Na+K+pump)
Found in all cells
Three subunits (α, β, and γ) α subunit has binding sites for: Na+, K+, ATP and Ouabain (inhibitory – used to treat hypotension)
ATP binding cassette(ABC) transporters:
An example of an ABC transporter. Cystic fibrosis transmembrane regulator (CFTR).
Explain primary and secondary active transport mechanisms with appropriate examples.
- transport is directly coupled to ATP hydrolysis (to move substances against their concentration gradient).
Secondary active transport (no ATP)
* Energy for the transport comes from the electrochemical gradient. The energy from one molecule is used to move another molecule(s) against its electrochemical gradient
e.g. 3Na+-Ca2+ antiporter
Describe osmosis.
diffusion:
solute is added to a solvent, solute particles will move randomly (Brownian motion) from area of high concentration of solute particles to areas of low concentration of solute particles (down their concentration gradient) until equilibrium is reached
osmosis:
*Diffusion of water across a semi-permeable membrane
*Membrane is freely permeable to water but not permeable to solute (see image)
*Water diffuses from a high water concentration to low water concentration (note: high water concentration = low solute concentration)
Define hydrostatic pressure.
*A difference in hydrostatic pressure between the 2 compartments is created, and it opposes osmosis.
*Hydrostatic pressure is the pressure exerted by a stationary fluid on an object – a “pushing force”.
Define osmotic pressure.
*The osmotic pressure of a solution is a measure of the tendency for water to move into that solution because of its relative concentration of non-penetrating solutes and water – a “pulling force”.
*Net movement of water continues until the opposing hydrostatic pressure exactly counterbalances the osmotic pressure.
Compare molarity and osmolarity.
Molarity
Number of molecules in a solution
Mol / L
(remember this useful equation: Mols = Mass / Mr)
Osmolarity = number of particles in a solution
Osm / L
The difference between molarity and osmolarity depends on the substance:
examples:
Glucose
Molecules DO NOT separate out in solution therefore molarity and osmolarity are the same.
Molar it’s = 5.5 mM/L
Osmolarity= 5.5mOsm/L
NaCl
Separates out into two different ions (Na+ & Cl-) therefore the osmolarity is double the molarity.
Molarity = 1 mol/L
Osmolarity = 2 osm/L
Define tonicity.
Tonicity = the effect the osmotic pressure gradient has on cell volume
* Cells change shape due to the net movement of water (into or out of the cell).
explain what would happen to a cell if it was placed in the following solutions:
Isotonic
Isotonic = the two solutions have the same solute concentration
therefore no net movement of water
Explain what would happen to a cell if it was placed in the following solutions: Hypotonic
extracellular: 150mOsm/L
intracellular: 300mOsm/L
therefore as the solute concetration of particles is lower outside- therefore it is more dilute and there is more water outside the cell
water moves into the cell causing it to swell
Explain what would happen to a cell if it was placed in the following solutions: Hypertonic.
extracellular: 600mOsm/L
intracellular: 300mOsm/L
hyperosmotic solution outside cell therefore water will move out causing the cell to shrink
osmolality and water balance disorders
*Osm per kg of body weight (Osm/kg)
*Useful for human / medical studies
*Normally about the same as osmolarity
*Normal plasma values 280-295 mOsm/kg
Osmolarity = osmoles per volume
Osmolality = osmoles per weight (typically kg)
Extra cellular fluid can be:
hypotonic (positive water balance): cells swell then undergo regulatory volume decrease (RVD).
hypertonic (negative water balance): cells shrink then undergo regulatory volume increase (RVI).
Describe the mechanism of contraction in skeletal muscle.
- Action potential propagates into the skeletal muscle cell.
2.Depolarisation of sarcolemma and T-tubules.
3.Activation of DHP receptors and Ryanodine receptors.
4.Calcium release from terminal cisternae of sarcoplasmic reticulum (SR).
5.Contractile machinery activated.
6.Calcium pumped back into SR (active process - requires ATP).
7.Calcium diffuses to terminal cisternae of SR ready to be released again.
Explain the sliding filament theory of muscle contraction, including the detailed sequence of events that occurs in a cross-bridge cycle.
when contracted:
z disk moves in
I band gets smaller
H zone gets smaller
A band stays same
Actin and myosin dissociate when ATP is bound by myosin.
ATP breakdown to ADP and Pi causes a change in the angle of the head region of the myosin molecule, this enables it to move relative to the thin filament.
This cycle is then repeated. This process is known as cross-bridge cycling.
Describe the role of calcium in muscle contraction, including triggering of contraction, release and re-uptake.
Propagation of (action potential) AP down into T-tubules
Activation of dihydropyridine receptors (DHPR) (T-tubules; conformational coupling with ryanodine receptors (RyR)).
Release of calcium from sarcoplasmic reticulum (SR).
Binding of Ca to troponin (conformational change tropomyosin).
Cross Bridge formation (Actin and Myosin; ATP).
Cross bridge cycling (Power Stroke; release of ADP + Pi).
Ca2+ removed from troponin restoring tropomyosin and Ca?+ taken back up by SR
rigor mortis
Rigor mortis is caused by depletion of ATP.
*ATP causes actin-myosin bridges to separate during the relaxation of the muscle.
*Without ATP to separate the cross-bridging skeletal muscles are locked in place.
*As part of the decomposition process, myosin heads are eventually degraded by cellular enzymes allowing release of the cross-bridges and the muscles to relax.
*Peak rigor mortis ~13hours after death
*Decomposition of myofilaments ~48-60hours after the peak of rigor mortis
Plot a classical experimental length-tension curve for a single muscle fibre and interpret it in terms of the sliding filament theory.
experiments initially conducted on isolated frog muscle fibre
clamp both ends and stretch the muscle fibre
sarcomere length:
between 2-2.5 is relaxed/optimum
phases:
latent/latency period
contraction phase
relaxation phase
single contraction: twitch
Skeletal muscles are classified as being fast or slow twitch based on speeds of sarcomere shortening.
*Morphological differences too:
Fast = white (lower myoglobin & capillary content)
Slow = red (high myoglobin & capillary content)
tetanus
Tetanic fusion frequency
Tetanus: The prolonged contraction of a muscle, caused by a rapidly repeated stimuli
TFF = the frequency of action potentials that are needed to not see summation and produce a smooth graded contraction as seen in normal muscle contraction.
Describe the ultrastructure of cardiac muscle.
10 μm diameter
100 μm length
Mechanical junctions:
fascia adherens
desmosomes
Electrical connections
gap junctions–
*Desmosome = mechanical junctions between adjacent muscle fibres.
*Gap Junctions = Electrical connectivity between adjacent muscle fibres.
*Highly organised contraction
*Pumps blood around cardiovascular systems
*Action potential initiated in Sinoatrial node (SAN) passes quickly through electrical syncytium – firing action potentials spontaneously
*Refilling of heart requires synchronised relaxation
