Physio

• Neurotransmitters


  Chemicals released by neurons that mediate communication within neuron-to-neuron or neuron-to-effector organ, inducing excitation or inhibition of postsynaptic target
• Neuromodulators


  Chemicals released by neurons that have little or no direct effects on their own but can modify the effects of neurotransmitters
• Chemistry of neurotransmitters


  • Small molecule transmitters (amino acids, acetylcholine, monoamines)
  • Large-molecule transmitters (neuropeptides)
  • Gas transmitters (nitric oxide, carbon monoxide)

  
• Receptors


  • Each chemical mediator has the potential to act on many subtypes of receptors
  • Receptors for many neurotransmitters are located on both presynaptic and postsynaptic elements
  • Receptors are grouped into two large families: ligand-gated channels (ionotropic receptors) and metabotropic receptors (G-protein-coupled receptors)
  • Receptors are concentrated in clusters on the postsynaptic membrane close to the endings of neurons that secrete the neurotransmitters specific for them
  • In response to prolonged exposure to their ligands, most receptors become unresponsive, they undergo desensitization (homologous or heterologous)
• Reuptake


  Process in which neurotransmitters are rapidly transported from the synaptic cleft back into the cytoplasm of the neurons are released, involving a high-affinity, Na+ -dependent membrane transporter
• After release of norepinephrine into the synaptic cleft, it is rapidly routed back into the sympathetic nerve terminal by a norepinephrine transporter (NET), and a portion is sequestered into the synaptic vesicles through the vesicular monoamine transporter (VMAT)
• Acetylcholine


  • Maybe excitatory or inhibitory
  • Found in the NMJ, Sympa and Para Preganglionic neurons, Para and some Sympa Post-ganglionic neurons, basal ganglia, large pyramidal cells of the motor cortex, gigantocellular neurons of the REA
  • Created by: Choline Acetyl- transferase from Acetyl CoA and Choline
  • Degraded by: Acetylcholinesterase into Acetate and Choline (1⁄2 of which will undergo reuptake)
  • Triggers REM sleep
  • Decreased levels in Huntington's dementia and Alzheimer's dementia
• Norepinephrine


  • NeuroMODULATOR in the CNS and NeuroTRANSMITTER in the PNS
  • Synthesized INSIDE synaptic vesicles
  • HALF-LIFE: 2 MINUTES (short compared to renin, aldosterone, corticosterone, and DHEA)
  • Primary NT from post-ganglionic sympa neurons
  • For arousal/wakefulness
• Epinephrine


  • Secreted mainly by the adrenal medulla
  • Greater Beta-2 action than NE
  • Relieve effects of bee sting by decreasing contraction of airway smooth muscles
• Dopamine


  • Secreted in the substantia nigra (fine-tunes movement)
  • Also secreted by the hypothalamus (PIF or PIH) to inhibit prolactin
  • D1 Receptor: activates adenylate cyclase using Gs protein; D2: inhibits adenylate cyclase using Gi protein
  • Decreased in Parkinson Disease, increased D2 in Schizophrenia
  • Schizophrenia can be due to abnormalities in the prefrontal lobes, frontal lobes and limbic system (hippocampus)
• Serotonin


  • Found in the median raphe of the brain stem, from tryptophan, converted to melatonin
  • Low levels association with depression
• Nitric Oxide


  • NO synthase converts Arginine to citrulline and NO
  • Permeant gas, inhibitory NT, vasodilator
• Glycine


  • Spinal cord main inhibitory NT
  • Increases Cl influx
• GABA


  • Brain main inhibitory NT (e.g. spiny neurons of the striatum, Purkinje Cells of the cerebellum)
  • Increases Cl- influx (GABAA) or K+ Efflux (GABAB)
  • Decreases anxiety: GABAA
  • GABA Receptors in the Retina: GABA A (ionotropic, ubiquitous), GABA B (metabotropic), GABA C (ionotropic, enriched in the retina)
• Glutamate


  • Brain main excitatory NT
  • Formed from reactive amination of Alpha-ketoglutarate
  • 3 Receptor subtypes Ionotropic (ligand-gated) including NMDA receptors, 1 subtype metabotropic
  • Activates NMDA receptors

  
• Opioid Peptide


  • Inhibits neurons in the brain
  • Involved in pain perception (e.g. enkephalin, endorphins, dynorphins; does NOT include morphine which is exogenous)
• Neurotransmitter Receptors


  • Metabotropic Receptors (G-protein Coupled Receptors)
  • Ionotropic Receptors (Ion-channel linked-receptors)
• Opioid Peptide Receptors


  • Come in 3 types: Kappa (analgesia, diuresis, sedation, meiosis, dysphoria), Mu (site of action of morphine, causes analgesia, respiratory depression, constipation, euphoria, sedation, meiosis, increased GH and prolactin), Delta (analgesia)
• Sensory modalities


  • Touch, pain and temperature
  • Vision
  • Hearing and equilibrium
  • Smell and taste
• Sensory receptors


  • Cutaneous mechanoreceptors
  • Proprioceptors
  • Thermoreceptors
  • Nociceptors
  • Chemoreceptors
  • Photoreceptors

  
• Cutaneous mechanoreceptors


  • Mediate responses to touch and pressure

  
• Proprioceptors


  • Relay information about muscle length and tension (muscles, tendons, joints)
• Thermoreceptors


  • Sensations of warmth and cold
• Nociceptors


  • Respond to potentially harmful stimuli such as pain, extreme heat, and extreme cold
• Chemoreceptors


  • Stimulated by change in the chemical composition of the local environment
  • Receptors for taste and smell as well as visceral receptors, sensitive to changes in the plasma level of O2, pH, and osmolality
• Photoreceptors


  • In the rods and cones in the retina respond to light
• Types of cutaneous mechanoreceptors

  • Meissner corpuscles
  • Merkel cells
  • Ruffini corpuscles
  • Pacinian corpuscles

  
• Meissner corpuscles


  Dendrites encapsulated in connective tissue beneath the epidermis of glabrous (non-hairy) skin, respond to slow vibration
• Merkel cells


  Expanded dendritic endings in epidermis of glabrous skin, respond to sustained pressure and touch
• Ruffini corpuscles


  Enlarged dendritic endings with elongated capsules in the dermis of glabrous and hairy skin, respond to stretch and fluttering vibration
• Pacinian corpuscles


  Largest cutaneous mechanoreceptor, in the dermis of glabrous and hairy skin, respond to fast vibration and deep pressure
• Types of nociceptors


  • Mechanical nociceptors
  • Thermal nociceptors
  • Chemically sensitive nociceptors
  • Polymodal nociceptors

  
• Mechanical nociceptors


  Respond to strong pressure (e.g. from a sharp object)
• Thermal nociceptors


  Respond to skin temperatures above 45°C or by severe cold (<20°C)
• Chemically sensitive nociceptors


  Respond to chemicals such as bradykinin, histamine, high acidity, and environmental irritants
• Polymodal nociceptors


  Respond to combinations of mechanical, thermal and chemical stimuli
• Aδ fibers


  Thinly myelinated, conduct at rates of ~12–35 m/s, responsible for first (fast) pain
• C fibers


  Unmyelinated, conduct at low rates of ~0.5–2 m/s, responsible for second (slow) pain
• Activation of Aδ fibers

  Releases glutamate, mediates the discriminative aspect of pain or the ability to localize the site and intensity of the noxious stimulus
• Activation of C fibers

  Releases a combination of glutamate and substance P, responsible for the delayed second pain (slow pain), which is the dull, intense, diffuse, and unpleasant feeling associated with a noxious stimulus