Signalling with the nervous system Flashcards
What is interesting about squid when studying axons?
Squids have a giant axon, which could be isolated to then measure action potentials through it.
How do neurons transmit electrical signals?
How can the resting potential be measured?
Describe an action potential?
They generate electrical signals based on the flow of ions across their plasma membrane through ion - channels. Under resting conditions, neurons also have a negative internal potential, the resting membrane potential.
The resting potential can be measured by recording the potential difference between the inside and the outside of the - cell, usually with a glass microelectrode.
The action potential, is a transient reversal of the resting membrane potential. Action potentials are propagated along the length of the axon and are the fundamental electrical signals that carry information from one place to another in the nervous system. Action potentials are ‘digital’ pieces of information that act as an all-or-nothing signal. These electrical signals depend upon ion fluxes across the nerve cell membrane. These ions fluxes are possible because of the non-uniform distribution of ions across the membrane that is the basis of the RESTING MEMBRANEPOTENTIAL.
Why is membrane potential essential?
A negative membrane potential is essential for the transfer of ions, solutes and other molecules in and out of the cell, generation of energy for cell movement or division.
What are the ion channels involved during action potentials
sodium and potassium ion channels
Ion Channels and Ion Transporters
Ions (e.g. Na+, K+) are charged, and can only pass through pores (channels) in the cell membrane or be carried by ion transporters to carry an ionic current or create a separation of ion charge
The channels are formed by protein molecules that span the membrane to provide routes for ionic current flow that gives the basis of RESTING and ACTION POTENTIALS
important channel is also Na/K ATPase (sodium pump)
What is involved in generating and maintaining the resting potential?
Na/k ATPase =active transport of 3Na+ out and 2K in to make the cell more negative.
Tandem pore domain k+ channel = passive transport
What is the membrane potential?
The membrane potential of any cell is the voltage across the cell membrane represented by the symbol Vm (sometimes as Em). Vm can be measured with a microelectrode that measures the potential difference between the inside of the cell and a reference (outside) The inside of the neuron is negatively charged with respect to outside. The resting potential in resting neurons is normally around -65 millivolts (b) (1mV = 0.001V)Vm=-65mV
The resting potential
The resting membrane potential is the result of a charge separation across the cell membrane. The charge separation is produced by the interaction of two gradients
1) An ionic concentration gradient
2) An electrical potentialgradient
The ionic concentration gradient
(accounts for 10% basal metabolic rate)
Ionic concentration gradients are established by the actions of ionic pumps. The sodium-potassium ATPase (sodium pump) breaks down ATP in the presence of internal Na+ releasing energy which drives the exchange of 3 internal Nations for 2 external K+ ions. The Na+/K+ pump ensures that K+ is concentrated inside the cell and that Na+ is concentrated outsidethecell
How could we measure the exact value of the equilibrium potential for each permeant ion species?
Each ion ahs its own equilibrium potential.
We could use the NERNST equation. This takes into consideration the ion charge, the temperature and the ratio of internal and externalconcentrations
The GOLDMAN-HODGKIN-KATZ equation
If the cell membrane were selectively permeable to only one ion species then Eion = Vm However Ex-80 mV, EN = +62 mV. In reality, the neuronal membrane is permeable to more than one species and the aggregate V is determined by the relative permeabilities of each species.
Under resting conditions the membrane has relatively HIGH PERMEABILITY TO K and LOW Na PERMEABILITY. The GOLDMAN-HODGKIN-KATZ equation gives the membrane potential from a given set of ionic concentrations inside and outside the cell PLUS the influence of the ionicpermeabilities
Important Points to Remember
Active transport establishes Na+ and K+ gradients.
Potassium is more concentrated inside. (100mM)
Sodium is more concentrated outside. (150mM)
Neuronal membrane potential depends on the ionic concentrations either side of the membrane.
(e.g. the higher the [K+]o , the lower the concentration gradient and the lower the Ek)
At rest the membrane is not equally permeable to all ion species but has selective permeability.
At rest the membrane has high permeability to K+, low permeability to Na+
At rest the Em is dominated by the combined influence of:
1. the outwardly directed K+ ionic [K+] gradient
2. large relative K+ permeability (Pk)
The importance of regulating external potassium
The neuronal membrane has high permeability to K+ and is therefore sensitive to changes in the concentration of extracellular potassium A 10 fold increase in [K+]o, from 5 to 50 mM reduces Vm from -65 to -17mV. This change to a less negative value is termed a depolarisation.
Low EM =Depolarisation
High Em (mV) = Hyperpolarisation
Increasing extracellular potassium reduces the Em, and depolarises neurons. All cells, including neurons can only survive brief changes to theirrestingEm
How could we buffer the changes in K+
The brain has evolved mechanisms to buffer alterations in [K+]o, The blood-brain barrier (bbb), limits movement of K into extracellular fluid of brain Within the CNS. Astrocytes possess K pumps that concentrate potassium intheircytosol.
How are electrical potentials generated across the neuronal membrane?
1) There are differences in the concentrations of specific ichs across the membrane.
2) The resting membrane is selectively permeable to some of these ions which move across the membrane influenced by the electrical and chemicalgradients
Alpha subunit on our sodium channel
The ion channel is formed by protein subunits that span the cell membrane and form a pore.
The pore has selectivity for Na+ ions
The pore is a voltage sensor, it opens and closes depending on the potential across the membrane
The alpha subunit is a binding site for TTX (tetrodotoxin),
Neosaxitoxin (NSTX) and Saxitoxin (STX): Paralytic Shellfish Poisoning
Local anesthesia also binds
Describe the structure of potassium channels
Potassium channels have a tetrameric structure in which four identical protein subunits associate to form a fourfold symmetric (C4) complex arranged around a central ion conducting pore (i.e., ahomotetramer).
What is spatial summation
What is temporal summation
*Spatial summation uses multiple synapses acting simultaneously
*Temporal summation occurs when one presynaptic neuron releases neurotransmitter many times over a period of time
Describe the two types of synapses
chemical synapse=Neurotransmitter release: carries the ‘message’ from one nerve cell to another, or muscle or gland cell Pre and Post synapses. Gap between cells is about 20 nanometres, Speed of transmission is several milliseconds
Can be excitatory or inhibitory and No loss of signal strength
electrical synapse= Transmission of electrical signal Between 2 nerves pr between nerve and effector target. Gap between cells is about 3.5 nanometres, Speed of transmission is nearly instantaneous, Excitatory only and Signal strength diminishes over time.
Describe signal transmission through a chemical synapse
The generation of an action potential in the presynaptic neuron. This electrical signal travels down the axon to the axon terminals, where it triggers the release of neurotransmitters.
Within the axon terminals, there are synaptic vesicles filled with neurotransmitters. These vesicles are located near the presynaptic membrane in specialized structures called active zones.
Calcium Influx: When the action potential reaches the axon terminal, voltage-gated calcium channels open, allowing calcium ions to enter the cell. The increase in intracellular calcium triggers the fusion of synaptic vesicles with the presynaptic membrane, leading to exocytosis.
The synaptic vesicles release neurotransmitters into the synaptic cleft through exocytosis. This process involves the fusion of vesicle membranes with the presynaptic membrane, causing the release of neurotransmitters into the synaptic cleft.
The synaptic cleft is a narrow extracellular space between the presynaptic and postsynaptic neurons. It acts as a barrier that neurotransmitters must cross to transmit the signal from the presynaptic to the postsynaptic neuron.
Neurotransmitters released into the synaptic cleft bind to specific receptors on the postsynaptic membrane. These receptors are typically ligand-gated ion channels, and their activation allows ions to flow across the membrane.
The binding of neurotransmitters to receptors generates postsynaptic potentials, which can be either excitatory (EPSP) or inhibitory (IPSP), depending on the type of ion channels activated.
The postsynaptic neuron integrates the excitatory and inhibitory signals received from multiple synapses. If the net effect is depolarization reaching the threshold, it may generate an action potential.
Neurotransmitter effects are terminated through various mechanisms, including reuptake into the presynaptic neuron, enzymatic degradation in the synaptic cleft, or diffusion away from the synapse.
postsynaptic receptor gate ion channels either directly or indirectly
Direct gating=neurotransmitter binds directly to ion channel itself. Ion channel is composed of different subunits, these subunits cluster together or have pore in the middle allowing the ion to pass through.
Indirect gating= Neurotransmitters bind to receptors. Second messenger systems, such as cAMP or protein kinases, play a key role, leading to changes in ion channel conductance and cellular responses. This mechanism allows for signal amplification and precise control of ion permeability, contributing to diverse physiological processes.
The Neuromuscular Junction
Good example of directly gated synaptic transmission
Using the frog NMJ, several scientists contributed fundamental discoveries to neuroscience
Understanding the fundamental properties of acetylcholine (Ach) release at the NMJ was a major landmark in biology.
Describe the synaptic transmission at a neuromuscular junction
The synaptic transmission at a neuromuscular junction (NMJ) is a specialized form of chemical synapse where a motor neuron communicates with a skeletal muscle fiber. This process involves the release of neurotransmitters, typically acetylcholine (ACh), and the subsequent generation of a muscle action potential. Here is an in-depth description of the synaptic transmission at a neuromuscular junction:
Motor Neuron Action Potential:
The process begins with an action potential traveling down the motor neuron, specifically its axon terminals.
Depolarization of Axon Terminals:
The action potential depolarizes the axon terminals of the motor neuron, leading to the opening of voltage-gated calcium channels.
Calcium Influx:
Calcium ions (Ca2+) enter the axon terminals due to the opening of voltage-gated calcium channels. This influx of calcium is critical for the release of neurotransmitters.
Neurotransmitter Release:
The rise in calcium levels triggers the fusion of synaptic vesicles containing acetylcholine with the presynaptic membrane, resulting in exocytosis.
Acetylcholine is released into the synaptic cleft.
Acetylcholine Binding to Receptors:
Acetylcholine diffuses across the synaptic cleft and binds to nicotinic acetylcholine receptors (nAChRs) on the sarcolemma (cell membrane) of the muscle fiber.
Endplate Potential (EPP):
The binding of acetylcholine to nAChRs opens ion channels, allowing the influx of sodium ions (Na+) and efflux of potassium ions (K+).
This results in the depolarization of the muscle fiber membrane, generating an endplate potential (EPP).
Generation of Muscle Action Potential:
If the endplate potential is of sufficient magnitude, it triggers an action potential that propagates along the sarcolemma and into the T-tubules (transverse tubules) of the muscle fiber.
Release of Calcium from Sarcoplasmic Reticulum:
The action potential in the T-tubules activates voltage-gated calcium channels in the sarcoplasmic reticulum (a specialized endoplasmic reticulum in muscle cells), leading to the release of stored calcium ions into the cytoplasm of the muscle fiber.
Muscle Contraction:
The increased concentration of calcium ions in the cytoplasm initiates the contraction of the muscle fiber by binding to troponin and facilitating the interaction between actin and myosin filaments.
Termination of Signal:
Acetylcholine’s action is terminated by the enzyme acetylcholinesterase, which breaks down acetylcholine into acetate and choline.
Choline is actively transported back into the presynaptic neuron and used to synthesize new acetylcholine.
Relaxation of Muscle Fiber:
The removal of calcium ions from the cytoplasm allows the muscle fiber to relax, and the process is ready to be repeated for the next contraction.
What are the two fundamental principles of synaptic transmission?
- There is a delay (synaptic delay)
- Neurotransmitter release is Ca2+ dependent
