3 - Excitable Tissues Flashcards
What are excitable tissues? And what are the major types?
- Tissues that utilise electrical signals that travel along cells and can be readily transferred from cell to cell
- Neurones and Muscle (skeletal, cardiac and smooth)
How do you record the membrane potential in a single cell?
Use a voltmeter with microelectrodes. Place one extracellularly and one intracellularly, then measure the potential difference
What is resting membrane potential?
Membrane potential of an excitable cell at rest. Membrane is polarised
Define polarised
2 sides are different charges
What happens during depolarisation
Membrane potential decreases in magnitude from RMP (inside of the cell becomes less negative)
What happens during repolarisation
- Restoration of the difference in charge
- MP increases in magnitude back towards RMP
- Inside of the cell becomes more negative
What happens during hyperpolarisation?
- MP increases in magnitude from RMP
- Membrane is more polarised (more negative)
What happens during hyperpolarisation?
- MP increases in magnitude from RMP
- Membrane is more polarised (more negative)
What are graded potentials? And what are their key characteristics?
- Occur when an excitable tissue is subjected to an excitatory/inhibitory stimulus
- Small changes in MP (1-30mv)
- Transient (lasting 10’s of ms)
- Proportional to size of stimulus
- Produce local not global effects (only effects part around the stimulus, not the whole cell)
Explain depolarising graded potentials
- Produced by an excitatory stimulus applied to the cell
- Causes a transient depolarisation of the membrane
Describe hyperpolarising graded potentials
- Inhibitory stimulus applied to the cell
- Causes a transient increase in the membrane potential
- More negative than the RMP
What are the general features of an action potential?
- Large, fast complex changes in MP by large excitatory stimulus
- Affects the whole cell (once initiated, travels over the whole cell)
- To get an AP, depolarising GP must be large enough to reach threshold (varies from cell to cell)
Describe the phases of action potentials
- **Depolarising phase: **period between threshold and the peak. Inside of the cell is positive compared to the outside
- Repolarising phase: Period between peak and RMP
- Hyperpolarising phase: Becomes more negative before returning to RMP
What are the typical membrane values at threshold and peak of action potential?
- Threshold: -65mV
- Peak: +30mV
Key differences between graded and action potentials
- AP always the same size, unlike GP (all or none principle. if threshold is reached, whole sequence occurs)
- APs are quicker (AP = few ms)
- Action potential propagation. Movement of AP. GP is localised.
What is conduction velocity?
- Speed of AP propagation is rapid
- Vary b/n cells (0.5-130 m/sec)
What is frequency encoding?
- APs encode info by frequency of APs
- Expressed in Hz
- Freq in excitable tissues = no. AP per second
Describe an experiment for frequency coding
- Measuring MP of a neurone in response to skin indentation by blunt probe
- As the probe is advanced, series of AP in neurone that last as long as skin deformation and have a consistent frequency
- Increase the force applied to the probe, higher freq of AP happens
- Therefore, higher stimulus intensity is encoded by a higher freq of AP
What are the normal intracellular and extracellular ion concentrations for major anions and cations in mammals
What is the functional significance of ion selective channels, resting channels and gated ion channels?
Bc ions are dissolved in aqueous ECF and ICF, can’t move through hydrophobic core of lipid bilayer so they move through these channels instead.
Explain voltage-gated ion channels and an example
- State of the gate is determined by MP
- Has a molecular sensor that measures MP
- Opens/closes depending on value
- E.g: VGNa+ and K+ channels in AP
Explain ligand-gated ion channels and an example
- Gated by binding of chemicals to a receptor closely associated with the channel
- Interaction between ligand/chemical and receptor enables high specificity in controlling ion channel opening
- E.g: acute sense of smell
- Important in a wide variety of physiological systems and are implicated in a number of diseases and actions of therapeutic drugs
Explain stretch-gated ion channels and an example
- Regulated by degree of stretch (mechanical deformation) exerted on membrane where they’re embedded
- Stetch produces a conformational shape change, opens the gate so ions pass
- Involved in initiating GP associated with sensory stimuli
Explain resting channels
- Ungated
- Open most of the time, not affected by stimuli
- Important for RMP
Describe the ionic-basis of the RMP
- At rest, membrane is freely permeable to K+ due to resting channels
- Higher concentration of K+ inside the cell and lower conc outside.
- K+ flows out of the cell down the concentration gradient
Explain why the resting membrane potential is slightly less negative than the equilibrium potential for K+
- Membrane is slightly leaky, so some Na+ passes through
- Making it slightly less negative
Ionic basis of action potential at threshold
- [Na] out > [Na] in. Therefore Na+ goes into the cell down conc gradient
- Inside of cell is negative, so EG attracts Na+ into the cell
- VGNa+ channels are closed at RMP, but are programmed to open during threshold.
- At threshold, membrane has increased permeability to Na+, so Na rushes into cell along CG and EG
- Membrane depolarises, as positive charge flows into cell. Inside of cell becomes less negative.
- Depolarisation causes more VGNaC to open and more Na goes into cell
- This positive feedback loop is responsible for the explosive nature of the depolarising phase of the action potential. Because the equilibrium potential for Na+ is around +56 mV, Na+ continues to flow into the cell even after the membrane potential reaches 0 mV and in fact continues on until it peaks at around +30 mV.
Ionic basis of AP at peak
- VGNaC close, some VGKC open
- CG and EG favours movement of K+ out of cell
- Net effect: influx of Na+ rapidly declines, more K+ leaving the cell along CG and EG
- As a result of declining influx of positive charge (Na+) and an increase in efflux of positive charge (K+), AP peaks and rapidly repolarises
- Repolarising phase is a direct consequence of K+ efflux
Ionic basis of hyperpolarising phase
- Consequence of slow closing of VGK+C
- Those channels + resting K+ channels causes MP to be higher than RMP
- Slow closing of VGKC responsible for hyperpolarising phase
Describe an experiment that could do to demonstrate that K+ is responsible for the resting membrane potential.
- Investigate the effects of varying conc of K+ in the solution bathing the cells on RMP
- Measure the RMP of 5 cells by placing a moveable electrode inside each of the cells in turn
- (In prac book)
Describe an experimental approach that you could use to demonstrate that Na+ influx is responsible for the depolarising phase of the action potential.
Investigate the effects of varying extracellular [Na+] on the magnitude of the depolarising phase of the AP
(Prac book)
Understand what the Goldman-Hodgkin-Katz equation is and how to use it to predict the membrane potential if you know the relative permeability of the membrane to K+ and Na+.
Explain why the Goldman-Hodgkin-Katz equation provides a more accurate prediction of membrane potential that the Nernst equation.
Nernst eq assumes that channels are only permeable to 1 specific ion species. While this equation takes into account that channels may be permeable to more than 1 ion species.
Explain why the Goldman-Hodgkin-Katz equation provides a more accurate prediction of membrane potential that the Nernst equation.
Nernst eq assumes that channels are only permeable to 1 specific ion species. While this equation takes into account that channels may be permeable to more than 1 ion species.
Explain the mechanisms of action potentials
- Initiation: AP initiated at axon initial segment (adjacent to axon hillock). This is because this part of the membrane has a lower threshold
- Propagation: AP travels down the axon, away from the soma to the axon terminal.
Explain how the mechanisms of action potential propagation differ between myelinated and unmyelinated axons and the implication that this has for conduction velocity.
Unmyelinated
* AP in membrane causes VGNaC to open in adjacent membrane
* Na+ goes into cell and initiates AP further along axon
* Conduction velocity is quite slow (0.5-2.5 m/s)
Myelinated
* Wrapped in thick myelin sheath
* Node of ranvier: gaps in myelin sheath, axon is exposed
* Heavy insulation from myelin enables VGNa+C to detect the voltage of AP in adjacent node (AP can jump from node to node)
* Called Saltatory conduction
* Therefore, slow propagation of AP along nodes, but very rapid saltatory communication between nodes
* Causes conduction velocity to be much quicker (12-130 m/sec)
What are refactory periods?
- Refactory period keeps AP moving in 1 direction
- Region that AP has just passed through becomes refactory (inactive) for a short time
- Difficult to initiate AP in this part (hence 1 direction)
Exaplin the ionic basis for absolute refactory periods
- When the second stimulus is applied, cell fails to produce AP
Caused by: - VGNaC hae opened then closed again
- They get “jammed”
- Called Na+ channel inactivation
Explain the ionic basis of relative refactory period
- Small AP that gradually increases in size as the delay between stimuli increases
- AP with reduced amplitude
- Caused by gradual recovery of VGNaC
- As more and more of these Na+ channels come out of inactivation, more and more of them can be opened by the stimulus and more and more Na+ can flow into the cell. Because Na+ influx is responsible for the depolarising phase of the action potential the greater the influx of Na+ the bigger the action potential.
