CTR week 7

• Nervous system (NS)


  Master controlling and communication system of the body. The NS cells communicate with each other by electrical and chemical signals that cause very rapid, almost 'instantaneous" responses. Three broad components: Sensors, Processors that integrate information, Response signals that initiate a responses by activating "effectors"

  
• How do nerve cells send messages?


  1. Sensors - monitor changes/events, in response to both externally derived, or internally generated, stimuli

  2. Processors that integrate information (in the CNS especially)

  3. Response signals that initiate a responses by activating "effectors"

  
• Nervous system organization - basic terminology


  Afferent neurons (sensory neurons) send signals into the central nervous system (CNS) for processing. The processed signal is sent out along efferent neurons to activate the required cellular response in effector cells. The afferent and efferent neurons form the peripheral nervous system (PNS). The PNS can be divided into the somatic motor division and the autonomic division. The autonomic divisions can be further divided into sympathetic and parasympathetic divisions.

  
• Neuron


  Nerve cell, the functional unit of the nervous system. Information flow is from the neuronal cell body to the axon terminals, via axons.

  
• Three functional types of neurons


  • Sensory Neurons
  • Motor Neurons
  • CNS Interneurons

  
• Cell Body


  Approx. 1/10 of the cell volume. Contains nucleus where genes are transcribed. Maintains 'well being' of cell, & involved in protein synthesis. Packaged proteins in vesicles are transported to other regions, along microtubules. Organelles include: rough endoplasmic reticulum (ER), mitochondria, Golgi apparatus.
• Dendrites


  Highly branched structures which receive incoming signals from other neurons. Excitatory (and inhibitory) synapses form on dendritic spines, increasing the surface area of the neuron, allowing multiple inputs from several neurons.

  
• Be aware of diversity – details not required at this stage, but note that one cell body in the CNS can have 200,000 connections from other cells that themselves exists in the billions. Our brain cells collectively operate at a level so complex that 'astronomical' is an apt term
• Axons


  Propagate action potentials (APs) along their length to their terminals, very rapidly, but along the axon surface, not via the microtubules (which transport nutrients etc.).
• Synapses


  The electrical signal transmitted along the axon is translated into a chemical signal before it is relayed across the synapse onto the target cell. In the target cell, an electrical signal is again generated.
• Glial cells


  Play supportive role in the nervous system. Communicate with neurons and amongst each other. Some nerve axons are myelinated by glial cells.

  
• Schwann cells


  Produce myelin sheaths, concentric layers of phospholipid insulating sheath wrapped around some axons.

  
• Oligodendrocytes in the CNS and Schwann cells in the PNS produce myelin. Nodes of Ranvier are exposed regions of axons; signals are forced to 'jump' from node to node, and this allows for fast AP transmission.
• Where speed of neural signalling is important, axons are myelinated. Why not, then, have all axons myelinated?
• The Resting Membrane Potential (RMP) is the difference in electrical charge that is maintained across plasma membranes. Tiny although this charge is, measured in millivolts, it is crucial to all cells, but is particularly relevant to the transmission of electrical signals along nerve fibres.
• ICF vs ECF ion & protein concentrations


  ECF: high [Na+], low [K+]. ICF: high [K+], low [Na+], plus possession of lots of anionic proteins.
• Active transport of solutes helps create & maintain differences in [solute], Na & K of relevance to RMPs

  1. Proteins cannot diffuse across cell membranes

  2. Result is that cells are kept in a state of chemical disequilibrium
• Na+-K+ ATPase pump


  Operates in all living cells, all of the time. Counters inward movement of Na+ and outward movement of K+. ATP dependent. Uses up to 1/3rd of calories we consume.
• Electrical disequilibrium


  At the cell membranes of all cells, a state of electrical disequilibrium exists because: 1) There is active transport of ions across the cell membrane, 2) ICF anions (incl. proteins) cannot easily diffuse out of the cell.
• Uneven distribution of major intra- and extracellular ions (mM)


  • K+ (ICF 150, ECF 5)
  • Na+ (ICF 12, ECF 140)
  • Cl- (ICF 10, ECF 105)
  • Organic Anions (ICF 65, ECF 0)
• Electricity- relevant basics


  1. Law of conservation of charge: the net amount of electric charge produced in a system is zero. b) Opposite charges attract and like charges repel. c) Energy is needed to separate charge. d) If separated, charges can move towards one another, the material through which they are moving is called a conductor. e) If the material prevents the movement of separate charges, the material is called an insulator. The cell membrane (being 'fatty') is a good insulator.
• The Electrochemical Gradient


  The net result of active transport, and containment of anions in the ICF, causes both a chemical gradient and an electrical gradient at the cell membrane. Na+ ions will move into the ICF along a [conc. ] gradient and an electrical attraction (+ve being attracted to –ve). The cell membrane is not (normally) very permeable to Na+, and it also a good insulator, meaning it can maintain a separation of charge.
• Measuring RMP


  RMPs are measured with micropipettes, containing conducting fluid, inserted just under the cell membrane. A voltmeter measures the difference in electrical charge between two points; this is the potential difference, measured here in millivolts (mV). Resting membrane potentials vary between cells; -70mV is a good representative figure to remember.
• Resting membrane potential


  The charge difference is localized to the membrane. The charge difference is tiny, but measurable (mV = 1/1000 of a volt). This charge is termed the Resting Membrane Potential (RMP); by convention, it indicates the state at the internal membrane surface, so RMPs are negative.
• K+ ions and the resting membrane potential


  K+ ions tend to diffuse out of cell, along a steep [ ] gradient. K+ ions do move out of cell, but the extent of this is limited by the attraction of any +ve charge to negative charge, being the intracellular anions, especially proteins. At equilibrium there is small net loss of K+; this alone would generate a small negative charge of ~-90mV at the
• Resting


  The membrane potential has reached a steady state and is not changing
• Potential


  The potential energy created by separated charge, measured in millivolts (mV) in biological systems
• The electrical gradient created by the active transport of Na+ and K+ ions is a source of stored or potential energy
• It is important to realize that the trapping of anions intracellularly plays a crucial role here (limiting K+ loss; to be discussed subsequently)
• K+ ions


  • They contribute the most to the resting membrane potential
• K+ ions and the resting membrane potential


  1. Pr- (proteins anions) trapped within cell

  2. K+ ions tend to diffuse out of cell, along a steep [ ] gradient

  3. K+ ions do move out of cell, but the extent of this is limited by the attraction of any +ve charge to negative charge, being the intracellular anions, especially proteins

  4. At equilibrium there is small net loss of K+; this alone would generate a small negative charge of ~-90mV at the internal surface of the membrane

  5. However, a lesser RMP of -70mV is more usual for reasons to be mentioned later
• Nernst Equation


  Derived under resting membrane conditions when the work required to move an ion across the membrane (up its concentration gradient) equals the electrical work required to move an ion against a voltage gradient
• If the intracellular concentration [K+]) = 150mmol/L & extracellular [K+] = 5mmol/L, the equilibrium potential EK = -90mV
• In the early 1900's Bernstein proposed that the RMP of nerve cells would approximate the diffusion potential of K+ (using the Nernst equation), but it was not until the 1930s that this was confirmed experimentally by Hodge and Huxley who experimented on giant axons found in squid
• If the membrane was permeable to Na+ only, the equilibrium potential for Na+ is ENa= +60 mV
• Most cells are ~40x more permeable to K+ than Na+. As a result, the RMP is much closer to EK (-90 mV) than ENa (+60 mV)
• In fact, for most cells the RMP is, in most cells, close to -70 mV because a small amount of Na+ leaks into the cell
• If Na+ was to continue leaking in along both electrical and chemical gradients and K+ out, over time the membrane potential would be destroyed
• The sodium-potassium pump plays its role, actively transporting: 3x Na+ out for 2x K+ in (via the Na+/K+ATPase pump)
• Na+/K+-ATPase


  Also known as an electrogenic pump because it helps maintain the concentration/electrical gradient