Resting membrane potential ~ -70mV - Membrane is polarized (ie) Electrical charge on the outside of the membrane is positive while the electrical charge on the inside of the membrane is negative
Changes in membrane potential: Terminology Depolarization: Inside of cell becomes less negative relative to outside (> 70 mv) Repolarization: Membrane returns to the resting potential ( 70 mv) after depolarization Hyperpolarization: Inside of cell becomes more negative relative to outside (< 70 mv) Graded potentials: Localized changes in membrane potential (either depolarization or hyperpolarization) - (eg) A change in membrane potential from -70 to -60mV = a 10 mv graded potential Action potentials: Rapid, substantial depolarization of the membrane ( 70 mv to +30 mv to 70 mv all in 1 ms) - Signal over long distances
The Structure of a Neuron Nerve impulse is generated here Direction of Impulse Nerve Impulse: An electrical charge that passes from one neuron to the next,and finally to an end organ, such as a group of muscle fibers
RESTING STATE Resting state
An action potential Serve as electrical signals in excitable tissues
Action potential Starts as a graded potential (Small localised change in membrane potential) Requires depolarization greater than the threshold value: 15-20 mv Once threshold is met or exceeded, the all-or-none principle applies The strength of stimulus is not coded by the amplitude of the AP, but by the frequency. - When a greater stimulus strength is applied to a neuron identical AP s are produced more frequently.
Action potential Overshoot All AP s are of the same duration (~ 2 msec) and amplitude (~ -70 to +30 mv) Hyperpolarization Starts as a graded potential (Small localised change in membrane potential) Requires depolarization greater than the threshold value: 15-20 mv Once threshold is met or exceeded, the all-or-none principle applies The strength of stimulus is not coded by the amplitude of the AP, but by the frequency. - When a greater stimulus strength is applied to a neuron identical AP s are produced more frequently.
Action potential The role of ion channels
Refractory period As stimulus intensity increases, the frequency of AP s increase Time between successive AP s is reduced Another AP can not be produced until the preceding one has finished Refractory period: Time during which the patch of axon membrane is unable to produce another AP
Value of the refractory period? - Allows propagation of action potential
The Velocity of an Action Potential Effect of myelination Action potential is faster in myelinated fibers Effect of neuron diameter Larger diameter neurons conduct nerve impulses faster Larger diameter neurons present less resistance to current flow
Conduction of action potentials in unmyelinated axons - Contiguous conduction Conduction speed: Nerve impulse travels 1 meter in 0.1s (100ms) = 10 meters/second
Neurons have cable properties This means that neurons can transmit charges through its cytoplasm ~ 1-2mm However these cable properties are poor Why? 1. There is high internal resistance to the spread of charges 2. Many charges leak out of the axon membrane
Myelinated axon Myelin sheath acts as insulation Prevents flux of ions across the membrane Nodes of Ranvier: Interruptions in the myelin sheath (~1mm apart) Ion channels are concentrated at the nodes of Ranvier This is where the AP s occur Cable properties mean the AP s jump from node to node Saltatory conduction Conduction is faster in myelinated than unmyelinated axons
Conduction of action potentials in myelinated axons - Saltatory conduction Conduction speed: Nerve impulse travels 1 meter in 0.007s (7ms) = 143 meters/second (14 times faster than in unmyelinated axon)
Multiple sclerosis is an autoimmune demyleinating disease of the CNS Myelin sheath Degradation of myelin sheath in multiple sclerosis Nerve cell MRI scan showing lesions in MS brain Muscle T-cells, macrophages & B-cells infiltrate the CNS and attack the myelin sheeth resulting in demyelination
Dysregulated conduction in a demyelinated nerve fibres in multiple sclerosis Normal Multiple Sclerosis Symptoms of MS: - Blurred vision -Muscle weakness -Ataxia Consequence of demyelination in MS - Loss of axonal conduction for neurons of the CNS and in clinical disability
The Synapse Synapse: Site of functional connection between a neuron and another cell CNS: Another neuron PNS: Another neuron or an effector cell in a muscle or gland
Synapses Point of communication between neurones Most synapses involve neurotransmitters Synapses can be: Excitatory Inhibitory The two types of postsynaptic potentials are: EPSP: Excitatory postsynaptic potentials IPSP: Inhibitory postsynaptic potentials
Glutamate generates an excitatory post-synaptic potential (EPSP) EAA (Glutamate) EAA Ca++ + + + + + + Glutamate (NMDA) receptor is a ligand-gated Ca 2+ channel
GABA generates an inhibitory post-synaptic potential MILLIVOLTS -50 GABA -60-70 THRESHOLD GABA Cl- -80 TIME GABA A receptor is a ligand-gated Cl - channel - - - - - -
Excitatory Postsynaptic potentials (EPSPs) EPSPs are graded potentials that can initiate an action potential in an axon EPSPs bring the RMP closer to threshold and therefore closer to an action potential
Inhibitory synapses and IPSPs Neurotransmitter binding to a receptor at inhibitory synapses: Causes the membrane to become more permeable to potassium and chloride ions Leaves the charge on the inner surface more negative (due to flow of K+ out of the cell and the flow of Cl - in) IPSPs bring the RMP further away from the threshold Thereby reducing the postsynaptic neuron s ability to produce an action potential
Summation A single EPSP cannot induce an action potential EPSPs must summate temporally or spatially to induce an action potential Temporal summation One pre-synaptic neuron transmits impulses in rapidfire order Spatial summation Postsynaptic neuron is stimulated by a large number of pre-synaptic neurons at the same time IPSPs can also summate with EPSPs, canceling each other out
Recording electrode
Recording electrode
Integration of EPSPs and IPSPs occurs here
Key steps in chemical neurotransmission 1. Synthesis 2. Storage 3. Release Action potential Ca 2+ influx NT release (Exocytosis) 4. Receptor binding & activation Generation of a postsynaptic potential 5. Inactivation Metabolism/Reuptake Pre-synaptic neuron Post-synaptic neuron
What happens on the pre-synaptic side? AP arrives at the nerve terminal Nerve terminal membrane is depolarized Depolarization causes voltage regulated Ca 2+ channels to open Ca 2+ influx Action potential Ca 2+ Ca 2+ [Ca 2+ ]i = 100 nm [Ca 2+ ]e = 1-2 mm (10,000 fold difference approx.) Ca 2+ enters the nerve terminal down the concentration gradient
What happens on the pre-synaptic side? Ca 2+ activates enzymes and proteins in the nerve terminal Synaptic vesicles fuse with the plasma membrane & release their contents into the synaptic cleft by exocytosis Action potential Ca 2+ Ca 2+ There is a time delay of 0.5ms in synaptic transmission Time needed for Ca 2+ to enter & cause exocytosis of transmitter
Neurotransmitters Amines: Catecholamines, Acetylcholine, Serotonin Amino acids: Glutamate, GABA and Glycine Neuropeptides Action potential Ca 2+ Generate EPSP or IPSP Ca 2+ Neurotransmitters can be either exicitatory or inhibitory - Amount of neurotransmitter released is proportional to the frequency of action potentials produced at the nerve terminal
Summary: The Nerve Impulse A neuron's RMP of 70 mv is maintained by the sodiumpotassium pump. Changes in membrane potential occur when ion channels open, permitting ions to move from one side of the membrane to the other. If the membrane potential depolarizes by 15 to 20 mv the threshold is reached, resulting in an action potential. Impulses travel faster in myelinated axons and in neurons with larger diameters. Saltatory conduction refers to an impulse traveling along a myelinated fiber by jumping from one node of Ranvier to the next. Action potential results neurotransmitter release The neurotransmitter can generate an IPSP or EPSP in the post-synaptic neuron