Session 3 membrane potentials, transmission

• Nerve cells have an electric potential across the cellular membrane. This is referred to as the membrane potential.
• resting membrane potential = -60 to -90 mV
• Polarized cell membrane structure?

  • Extracellular high Na + - positive charge
  • Intracellular high K + - negative charge
• Why is intracellular part of the cell membrane of negative charge even though there is high K+?

  The interior of the excitable cell contain protein and phosphate in the form of negatively charged anions.
• Site of action potential initiation?

  Axon hillock (has high density of voltage gated sodium channels)
• Depolarized state of cell membrane is characterized by?

  • Opening of voltage gated Na channels
  • Influx of 3 Na +
  • Makes interior more positive
• Repolorized state of cell membrane is characterized by?

  • Opening of voltage gated potassium channels
  • Efflux of 2 K +
  • Tries to attain the resting membrane potential
  • causing the voltage to become negative again.
• In many cases, the membrane potential becomes even more negative than the resting potential for a brief period; this is called hyperpolarisation.
• Function of myelin sheath?

  Conduction of APs
• Schwann cells produce myelin sheath
• When is the threshold for an action potential reached?

  when the opening voltage-gated sodium channels stimulate other channels to open.
• In the Central Nervous System, an action potential is only produced if the sum of all of the inputs is enough to depolorise the neurone above threshold.
• When a single action potential reaches the sensory nerve synapse it does NOT generate an action potential in the motorneuron. There is only a small depolarisation of 5-10 millivolts in the motor neurone. This is called an excitatory post synaptic potential or EPSP. This is the result of increased membrane permeability to sodium.
• Spatial Summation occurs when there is convergence of several inputs synapses onto a post-synaptic cell.
• Temporal summation occurs when there are high frequency bursts of action potentials.
• How do local anesthetics work?

  Local Anaesthetics bind to specific site on voltage-gated sodium channels on the intracellular side of the receptor. This prevents sodium entry and Action Potential generation.
• Reduced extracellular sodium (hyponatremia) diminishes sodium influx through the voltage gated sodium channels and therefore reduces the amplitude of an action potential and slows the opening of voltage-gated channels along the length of the axon.
• Disease states affecting conduction of the action potential in the Central Nervous System?

  • Multiple sclerosis - all CNS nerves
  • Devic’s disease – optic and spinal cord nerves only
• Disease states affecting conduction of the action potential in PNS?

  • Guillain Barre syndrome
  • Charcot Marie Tooth disease
• breakdown or damage to a structure called the myelin sheath - demyelination
• Classification of demyelination?

  • Demyelinating myelinoclastic - myelin is destroyed by toxic substances, chemicals, or autoimmune reactions.
  • Dysmyelinating leukodystrophic - myelin is inherently abnormal and degenerates.
• SANS and PANS act on neurons that are present in the wall of the gut. These neurons are considered to form the enteric nervous system (ENS)
• ENS located in the submucosal plexus (Meissners plexus) and the myenteric plexus (Auerbachs plexus).
• Sympathetic nervous system - Thoraco-lumbar outflow - T1-L2/3
• General arrangement of the SANS

  The sympathetic ganglia (paravertebral ganglia) form two parallel trunks of interconnected ganglia either side of the vertebral column.
• Some exceptions to this general arrangement of SANS?

  • Preganglionic fibres to abdominal structures form the splanchnic nerves which synapse in either the coeliac, superior and inferior mesenteric ganglia.
  • Innervation of the adrenal medulla. Preganglionic fibres in the splanchnic nerves synapse directly with chromaffin cells
• Parasympathetic NS - cranio-sacral outflow
• Acetylcholine (ACh) is synthesised from choline and acetyl-CoA Reaction is catalysed by choline acetyltransferase.
• Some of the ACh is degraded by cytoplasmic acetylcholinesterase
• Cholinergic receptors my be muscarinic or nicotinic
• 5 types of muscarinic receptor?

  • MI – essentially neural receptors, CNS, PNS parietal cells. Mediate excitatory events by reducing K+ conductance resulting in hyperpolarization.
  • M2 – cardiac - work by increasing K+ conductance.
  • M3 – glandular and smooth muscle – mainly excitatory e.g. increasing secretions and contraction of visceral smooth muscle. NB may also relax some vascular smooth muscle via the production of nitric oxide.
  • M4/5 – located mainly in CNS
• types of nicotinic receptors?

  • Muscular
  • Ganglionic
  • CNS
• Noradrenaline is synthesized by dihydroxyphenylalanine (DOPA) and dopamine from tyrosine.
• Noradrenaline is also inactivated by the enzymes MAO and COMT
• Adrenoreceptors

  α: Noradrenaline>Adrenaline>Isoprenaline

  β: Isoprenaline>Adrenaline>Noradrenaline
• -

  A) alpha 1

  B) beta 2

  C) beta 1

  D) alpha 1