Why is studying ion channels important? What can malfunctioning ion channels lead to?
We are controlled by electrical impulses. If there's a change in the impulse it will change the way the processes work which will lead to disease. Ion channels are gated in the membrane that allow ions to flow through the gates, which allows for an electrical impulse/movement. All currents are made up of ion channels getting together. It's important to understand how gates work, because if they’re not working it will disrupt the current of the system. Malfunctioning ion channels can lead to diseases such as cystic fibrosis.
What are the key experimental techniques used to measure current flow through ion channels? Describe them.
1. Patch clamps - direct recording of ionic currents from cell surface ion channels. They measure ionic flow through plasma membrane ion channels. 2. Planar Lipid Bilayer technique - direct recording of ionic currents from intracellular ion channels.
What types of information can we obtain from single channel measurements?
1. WHAT OPENS THE CHANNEL. Can be: Voltage: Changing membrane voltage in depolarizing (+ve) or hyperpolarizing (-ve) direction eg voltage-gated Na+ or K+ channels Ligand: Neurotransmitter binds and activates from outside cell eg Glutamate receptor or a 2nd messenger binds at cytosolic surface and activates the channel e.g. Ryanodine receptor Stretch: Mechanosensitive channels Light: Channelrhodopsin 2. SINGLE CHANNEL CONDUCTANCE = how 'good' a channel is at letting current through 3. WHAT IONS FLOW THROUGH THE CHANNEL [ion selectivity] 4 INHIBITORS OF THE CHANNEL - Tetrodotoxin (Na+ channels) - Tetraethylammonium (K+ channels)
Give examples of channel mutations that result in alterations in single channel function and cause pathologies.
Intracellular calcium levels are involved in life and death situations. The RYR is a macromolecular complex involved in calcium movement into the cell to allow muscle contraction.RYR2 is cardiac-muscle, RYR1 skeletal muscle. RYR1 channel mutations are associated with Malignant Hyperthermia: • Pharmacogenetic disorder of skeletal muscle - Severe reaction to commonly used anaesthetics and depolarising muscle relaxants - First manifestations of MH occur in the operating room - Fatal if untreated • Symptoms = Muscle rigidity, High Fever, Increased acid levels in blood and other tissues, Rapid hr Underlying mechanism of MH = Point mutations in the gene coding for RYR1 Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inheritable autosomal condition. • Symptoms = Dizzy spells, fainting episodes, sudden cardiac death. • The arrhythmia displayed by CPVT patients is characterised by ventricular tachycardia that occurs with stress or exercise. • Underlying mechanism of CPVT = 69 point mutations were identified in the RYR2 gene when patients were screened for CPVT1
Define Inhibitory post synaptic potential (IPSP).
A net flow of negative ions hyperpolarises the cell (further from the threshold).
A neurone will fire when its membrane potential crosses the action potential threshold. What 3 things does this depend upon?
1. The inherent excitability of the neurone (the no. of ion channels expressed, excitatory and inhibitory) 2. The frequency or amount of incoming excitatory impulses (from one or many synaptic connections). 3. The frequency or amount of incoming inhibitory impulses (from one or many synaptic connections).
What is the role of IPSPs in the nervous system.
Inhibitory impulses can PREVENT a neurone from firing an AP, whereas without it, the neurone would fire. This can be used to produce rhythmic behaviour, such as tail wagging in tadpoles for movement, by excitation and inhibition of a neurone. This = RECIPROCAL INHIBITION, (as one side is inhibited the other is excited/fired to produce back and forth.) Another ex of inhibition modulating a neural system is PAIN. The stimulus causes an AP in a sensory neurone. This has a +ve excitatory effect on the pain neurone. There's also an inhibitory system through descending pain modulation via an inhibitory interneurone which desensitises the body to pain e.g. small cut (paper cut) can forget about the pain when completing a task
What is the importance of synapses in computation, rectification and plasticity?
COMPUTATION = As summation of multiple PSPs is required to achieve threshold. Integration acts as a decision making process based on EPSP and IPSP input. RECTIFICATION = As chemical synapses transmit impulses in one direction only, this rectification serves to channel information (give direction to). PLASTICITY = Controlled changes in the amount of transmitter released, the number of receptors present and the efficiency of the inactivation process provide a mechanism for adaptive plasticity (LTP, long term potentiation, and LTD, long term depression). This control is provided in part by neuromodulators such as the Encephalins. These small peptides modulate the transmission of pain at the level of the spinal cord. It's also involved in learning and memory.
Define the term 'plasticity' applied to neural networks and explain their importance in the nervous system (with some examples).
In memory and learning. Stronger synaptic connections which means easier/better synaptic transmission. Stronger synaptic connections come from, more vesicles, greater excitability, more receptors, more parallel synapses. This can mean particular stimuli illicit a strong memory. In addiction: 1. Overstimulation of pleasure pathway 2. Body responds by turning down transmission (reduced vesicles) or by turning down reception (reduced receptors) 3. Normal dose insufficient so more taken to overcome reduced transmission 4. Body further attenuates transmission 5. New increased dose insufficient so more taken to compensate
Define the term 'convergence' applied to neural networks and explain their importance in the nervous system (with some examples).
Information from multiple neurones are received by a single neurone. The more dendrites a neurone has, the higher the degree of convergence. Mammalian brain ranges from 1 to 100,000 inputs per neurone. Motor neurones can receive convergent synaptic inputs from: 1. Sensory neurones in the skin 2. Stretch receptors in muscle fibres 3. Proprioceptive joint receptors 4. Descending neurones 5. Ganglion cells in the eye
Define the term 'divergence' applied to neural networks and explain their importance in the nervous system (with some examples).
Information from a single neurone is passed to a number of other neurones simultaneously and without loss of signal strength. Multiple variations of this exist: 1. Proprioceptive info about a muscle or joint can be diverged to several different other neurones, potentially each with different functions 2. Sensory info arriving at the somatosensory cortex can be diverged widely through the cortex.
Define the term 'feedback' applied to neural networks and explain their importance in the nervous system (with some examples).
Local neurone feedback -
As N1 is excited more, this information is passed to N2. If N2 crosses threshold it fires and so inhibits its target, and feeds back inhibition to N1. Therefore N1 is moderated by negative feedback from N2.
What are the 4 main mechanisms of spinal injury?
Flexion Extension Compression Combination
What are the steps for managing a spinal injury? (HINT: there's 5)
1. Airway and Breathing, get help
2. Stabilise the spine, especially neck
3. Hard collar
4. Log roll to get onto spinal board
5. Immobilisation is key to preventing worsening of initial injury.