Pathologies Associated with Extracellular Potassium Levels and Synapse Functions

Pathologies Associated with Extracellular Potassium Levels

High Levels of Extracellular Potassium (K)

• Consequences of High K Levels:

  • Lowers the "incentive" to move due to a less steep concentration gradient.

  • The less steep gradient means that potassium does not "want" to leave the cell as much.

  • Results in a resting potential that is less negative than normal.

  • This change can make voltage-gated sodium (VG Na) channels inactive even before they open.

  • As a result, it becomes difficult or impossible to generate an action potential (AP).

• Extracellular Fluid (ECF) Ion Levels:

  • ECF potassium levels are typically very low, making them more susceptible to changes than intracellular potassium levels.

  • Even a slight change in extracellular potassium levels (as little as 1-2 mmol) can lead to significant physiological effects.

• Potential Causes:

  • Medications that affect potassium regulation.

  • Sodium (Na) and potassium (K) usually exchange in opposite directions across membranes.

  • In cases of spinal injury, there can be atrophy-related potassium release from muscle into the bloodstream.

Low Levels of Extracellular Potassium (K)

• Consequences of Low K Levels:

  • Higher incentive for potassium to leave the cell, demanding a stronger concentration gradient.

  • Results in a more negative resting potential.

  • Requires a greater stimulus to trigger action potential generation.

  • Again, this can render action potentials difficult or impossible to generate.

Target Cells for Action Potentials

• Types of Target Cells:

  • Skeletal Muscle: innervated by somatic motor neurons

  • Smooth Muscle

  • Cardiac Muscle

  • Gland Cells (epithelial)

  • Autonomic Motor Neurons

  • Other Neurons: including sensory and interneurons

Types of Synapses

1. Electrical Synapse

• Characteristics:

  • Involves gap junctions between neurons, eliminating the presence of a synaptic cleft.

  • Allows electrical signals (ions) to move directly between cells.

  • Common locations include certain smooth muscle cells and cardiac muscle cells.

2. Chemical Synapse

• Components:

  • Pre-synaptic membrane/terminal

  • Synaptic cleft

  • Post-synaptic membrane

• Functionality:

  • Allows for the integration of multiple inputs.

  • Features both summation of signals and varied response times.

  • Electrical synapses are quicker and more reliable, while chemical synapses allow for complex integration and signal processing.

Events at a Chemical Synapse

1. An action potential (AP) travels down the axon and arrives at the axon terminal.

2. Depolarization of the pre-synaptic membrane causes voltage-gated calcium (Ca) channels to open.

3. The influx of calcium triggers exocytosis of neurotransmitter vesicles.

4. Neurotransmitters bind to receptors on the post-synaptic membrane, inducing graded potentials in the target cell.

5. Neurotransmitter is released into the synaptic cleft.

6. Following action, neurotransmitter is either removed or inactivated, concluding the synaptic transmission.

Types of Synapses in Detail:

• Excitatory Synapse:

  • Neurotransmitter binding causes depolarization towards the threshold potential, making it more likely for the target cell to fire an AP (excitatory post-synaptic potential, EPSP).

• Inhibitory Synapse:

  • Neurotransmitter binding results in hyperpolarization away from threshold, making it less likely to fire an AP.

Receptors and Channels

Ligands

• Definition: A ligand is a chemical signal that binds to a membrane receptor, facilitating communication between cells.

• Types of Ligands:

  • Neurotransmitters

  • Hormones

  • Neurohormones

Receptor Types

1. Ligand-Gated Ion Channels:

   • Receptors that directly alter membrane permeability when a ligand binds and changes the shape of the receptor.

   • Result in rapid changes in membrane permeability and immediate alterations in ion current.

2. Receptors that Function as Enzymes:

   • Upon ligand binding, the receptor undergoes a conformational change that triggers intracellular reactions.

   • This mechanism typically has a longer time course than immediate ion channel opening, ultimately leading to significant activity changes in the target cell.

Neurotransmitters

• Definition: A neurotransmitter is a chemical released from an axon into the synaptic cleft at a chemical synapse.

• Example - Acetylcholine (Ach):

  • Locations: Peripheral nervous system (PNS), somatic motor neurons at neuromuscular junctions (NMJs), autonomic neurons, and parasympathetic neurons.

  • Mechanism: Reuptake of broken parts for recycling is common post-activation.

Group of Neurotransmitters: Catecholamines

• Overview: Catecholamines are produced by modifying the amino acid tyrosine, functioning as neurotransmitters or neurohormones.

• Types of Catecholamines:

  • Dopamine:

  • Locations: Basal nuclei of the brain.

  • Functions: Critical for movement control (e.g., Parkinson's disease), plays a role in the reward system (including mechanisms of drug abuse).

  • Pathologies related to dopamine: Parkinson's disease, schizophrenia, cocaine addiction, etc.

  • Norepinephrine & Epinephrine (Adrenaline):

  • Locations: Primarily in the PNS and involved in autonomic and sympathetic nervous responses (e.g., hypertension).

  • Mechanism: Activation of adrenergic receptors influenced by norepinephrine (NE) and epinephrine (E).

    • Receptor types: α-adrenergic and β-adrenergic receptors.

    • Clinical connection: β-blockers are often used to manage hypertension.

  • Serotonin:

  • Origin: Modified from the amino acid tryptophan.

  • Locations: Found in the CNS and PNS, crucial for promoting feelings of well-being.

  • Mechanism of inactivation: Typically through reuptake into the pre-synaptic terminal.

  • Related Concept: The gut-brain axis highlights interactions between gastrointestinal function and mental states.

  • Endorphins & Enkephalins:

  • Classification: Both are peptides and belong to a family of proteins.

  • Locations: Primarily within the CNS, they serve functions as natural pain reducers due to their analgesic properties.