Basic Principles Flashcards
First messengers
Signalling molecules released into the extracellular fluid with the aim of affecting functioning of other cells
Neurotransmitters
Secreted by a neurone to affect another excitable cell across a synapse eg. acetylcholine
Hormones
Secreted by glands and enter the bloodstream to reach their target cells or organ eg. insulin, adrenaline
Autocrine molecules
Act on the cell type that has secreted it eg. monocytes/macrophages, Interleukin
Paracrine molecules
Act on neighbouring target cells in close proximity eg. NO (nitric oxide)
How do cells recognise first messengers?
Receptors (cell-surface or intracellular)
- First messenger (agonist) combines with the receptor
- Receptor is activated
- Cellular response is activated (signal transduction pathway)
Ion channel linked receptors
- Ach binds to receptor -> ion channels open
- Ions can enter the cell, causing depolarisation or hyper-polarisation of the membrane
- Results in cellular effects
G-protein linked receptors
- Link receptor to effector
- 3 sub-units: alpha, beta, gamma
- Associates with guanosine-based molecules
- Active form (influencing cell function) = GTP
- Inactive forum (bound to receptor portion) = GDP
- FM associates with receptor portion
- Initiates dissociation of G-protein from receptor portion
- Splits into alpha sub-unit and beta+gamma sub-unit
- Alpha sub-unit moves through cell locating target enzyme
- Can either increase or decrease enzyme activity in order to influence levels of SM
Diffusion
Movement of molecules from high to low concentration.
- Small molecules
- Hydrophobic molecules
eg. fatty acids, CO2, O2
Osmosis
Diffusion of water from high to low concentration through a semi-permeable membrane.
Rate of diffusion
- Size of concentration gradient
- Permeability of membrane to substance
- SA of membrane
- Molecular weight of substance
- Diffusion distance
Facilitated diffusion
Movement of molecules down their concentration gradient but a membrane-bound protein is necessary to facilitate their passage (carrier and channel proteins)
eg. glucose, amino acids, ions
Active transport
Transport of substances against the concentration gradient. ATP is required
- Primary : carrier protein uses energy directly from ATP hydrolysis eg. sodium-potassium pump
- Secondary : uses energy stored in the concentration gradients of ions eg. sodium-glucose transporter
Vesicular transport
- Exocytosis : cellular materials exit the cell
- Endocytosis : materials are brought into the cell eg. phagocytosis, pinocytosis
Resting membrane potential
- During cell development, number of K+ = number of A-
- There is a conc gradient for K+ , so it diffuses out of the cell
- There is also a gradient from A-, but they are too large to leave so remain inside
- Chemical and electrical gradient balance out (electrochemical equilibrium)
- Less K+ inside the cell than outside and the same amount of A- inside
- Therefore, cell is negatively charged on the inside compared to the outside
REm of different cell types
- Nerve cells : -70mV
- Smooth muscle cells : -40mV
- Skeletal muscle cells : -90mV
Nernst equation
- Equilibrium is established at the point at which the attraction of the negative charges inside the cell (caused by A-) precisely counter the outward driving force of K+ conc gradient
- Potential at which this occurs is equilibrium potential for K+ (Ek)
- Used to calculate the equilibrium potential for any membrane permeant ion (determines contribution of particular ion to REm)
- Ek value not the same as REm (other ions contribute to REm)
Potential changes
- Cell is negative on the inside (at rest) = polarised
- Cell is positive on the inside = depolarised
- Cell returns to normal state (negative inside) = repolarisation
Local potentials
- Produced when neurone is stimulated
- Na+ channels open and Na+ flow into the cell (depolarisation)
- Vary in size depending on how many channels open
- Decline as they get further from point of stimulation
- Do not depolarise the entire length of the neurone
Threshold potential
- The soma contains an area of membrane called the trigger zone; has a very high density of Na+ channels
- If local potentials are strong enough to reach this zone, they can trigger an AP
- Membrane potential at which this occurs is called the threshold potential
Action potential
- Rapid and uniform electrical signal conducted down (along) a cell membrane
- Stimulus causes Na+ channels to open, causing an influx of Na+
- Depolarisation occurs; inside of the cell becomes more positive
- Repolarisation begins; Na+ channels close and K+ channels remain open. This prevents any more Na+ from entering, but still allows K+ to leave. Inside of cell becomes more negative and REm is reestablished. Cell is polarised. K+ channels close
Hyperpolarisation
Charge inside cell falls below REm at the end of repolarisation; K+ channels take longer to close than Na+ channels, letting slightly more K+ out than Na+ entered. Inward diffusion of Na+ through leakage channels bring Em back to normal
Refractory period
- Absolute refractory period : Na+ channels are shut and inactivated; impossible to open; impossible to stimulate the membrane to depolarise again
- Relative refractory period : lasts until after hyperpolarisation; Na+ channels may be open, but as K+ channels are also open it requires a greater stimulus; difficult to stimulate the membrane to depolarise again
Propagation of AP in a myelinated neurone
- Not every part of the axon has to depolarise
- Gaps in myelin; Nodes of Ranvier
- Signal jumps from node to node
- Faster AP propagation; saltatory conduction
Synaptic transmission
- Depolarisation of the pre-synaptic bulb opens voltage-dependent Ca2+ channels
- Ca2+ ions enter the cells
- Influx of Ca2+ causes exocytosis of the vesicles containing the neurotransmitter
- Ach is released from the pre-synaptic membrane
- Ach diffuses across the synaptic cleft and reaches receptors in the post-synaptic membrane
- Ach interacts with ligand-gated ion channels permeable to Na+
- Ion channels open and Na+ flows into the post-synaptic cell
- Depolarisation of the post-synaptic cell occurs
Ionotropic receptors
- Ligand-gated
- Cause a rapid opening of ion channels resulting in depolarisation or hyperpolarisation of the post-synaptic cell membrane
- Mediate fast ionic synaptic responses (milliseconds)
Metabotropic receptors
- G-protein coupled
- Initiate a wide variety of cellular responses
- Mediate slow biochemically-mediated synaptic responses (seconds-mins)
Different effects of the same neurotransmitter
Ach in skeletal and cardiac muscle:
- Nicotinic (ionotropic) : neuromuscular junction of skeletal muscle muscle; activates muscle fibres by causing rapid depolarisation; stimulation
- Muscarinic (metabotropic) : neuromuscular junction of cardiac muscle; activates G-protein sequence, ultimately resulting in K+ expulsion and membrane hyperpolarisation; inhibition
Excitatory and inhibitory post-synaptic potentials
- EPSP : brings the membrane potential closer to the threshold for an AP. If threshold is exceeded, AP is generated
- IPSP : causes hyperpolarisation and brings membrane potential away from threshold for AP, making it more difficult to generate
Summation
- A single post-synaptic cell may interact with multiple other cells, therefore EPSPs can ‘add up’ (summation)
- Temporal summation : EPSPs arrive rapidly in succession, subsequent EPSP adds to amplitude of preceding EPSP and so on, therefore post-synaptic membrane is brought closer to threshold; AP more likely
- Spatial summation : post-synaptic cell is stimulated by multiple pre-synaptic end bulbs at once, so post-synaptic membrane is closer to threshold; AP more likely
