Signalling II - Electrical Signalling and Neurotransmission

Electrical Signalling

  • Membrane Potential

    • Definition: Difference in voltage between the interior and exterior of the cell.

    • Typically -70 mV at rest but can vary.

  • Passive Ion Transport

    • Determined by the electrochemical gradient.

    • Can be affected by membrane potential (positive inside vs. negative inside).

Ion Gradients and Membrane Potential

  • Ion Gradients:

    • The membrane potential arises due to ion gradients and the charges of these ions.

    • “Fixed anions“ cannot move freely across the membrane. Thus they influence the membrane potential by balancing out the positive charges.

  • Equilibrium Potential:

    • Equilibrium potential is the membrane potential at which the net flow of a particular ion across the membrane is zero, meaning that the concentration gradient and the electrical gradient are balanced.

    • Calculated using the Nernst Equation:

      • Needs to know: concentration of the given ion in and out of the cell, charge of the ion, temperature in Kelvin, and several constants namely R gas constant, Faraday’s constant.

    • Example:

    • For K+: V=-90{ mV}

    • For Na+: V=+60m{V}

Membrane Potential Calculation

  • The resting potential (which comprises of the equilibrium potential of all permeable ions) arises mainly due to K+ imbalance (-70mV)

  • This is because most cells are more permeable to K+ than other ions (“leak channels“). Thus, the resting potential is closer to K+ ion equilibrium potential.

  • Goldman-Hodgkin-Katz Equation (GHK):

    • Calculates the membrane potential based on multiple ions.

    • Expression:

    • Where permeability ratios are crucial: PK>>PCl>>PNa (at resting potential), with K being the most permeable, followed by Cl, followed by Na.

    • The Ernest equation is a modification of the GHK equation.

Action Potentials in nerve cells

  • Characteristics:

    • Arise from the action of voltage-gated Na+ and K+ channels.

    • Depolarization initiated by opening Na+ channels, leading to an influx of Na+ ions.

    • After reaching the peak, K+ channels open leading to repolarization.

    • Phases of Action Potential:

    • Rising phase (depolarization): inward flow of Na+, raising the membrane potential towards equilibrium for Na+ which is +60mV

    • Overshoot (K+ channels open after a delay),

    • Falling phase (repolarization): K+ channels open following depolarisation, allowing K+ ions to exit and restore to resting potential -70mV.

Neurotransmission

  • Mechanism:

    • Action potential is propagated along the axon of the presynaptic cell.

    • Voltage-gated Ca2+ channels trigger neurotransmitter (e.g. acetylcholine) release at the synapse.

    • Post-synaptic ligand-gated channels respond to released neurotransmitters. Electrical signalling is enhanced at excitatory synapses and dampened at inhibitory synapses.

    • Sequential activation of Na+ and K+ channels in the post-synaptic cell allows the propagation of action potential.

  • Types of ligand-gated Ion Channels:

    • Ionotropic glutamate Receptors (found at excitatory synapses):

    • Respond to glutamate, allowing Na+ and Ca2+ into the post-synaptic cell, promoting excitatory signals.

    • Note that: ligand-gated channels have inverted topology of voltage-gated channels (see figure in Anki) - very similar but inverted.

    • GABAa receptors are inhibitory

    • They respond to the neurotransmitter GABA, allowing Cl- ions into the post-synaptic cell, which dampens excitation by leading to a hyperpolarizing effect, ultimately inhibiting neuronal activity.

      Structure of the GABA receptor. Notice the cys-loop receptor

    • Nicotinic Acetylcholine receptors are excitatory ligand-gated channels. Upon binding of acetylcholine, they open to allow Na+ influx which is critical for both nerve-to-nerve and nerve-to-muscle communication. It also has a cys-loop receptor.

Neuromuscular Junction (NMJ)

  • After action potential, pre-synaptic neuron releases acetylcholine which is then received by receptors in muscle cells, initiating muscle contraction.

  • Components:

    • The NMJ includes voltage-gated Ca2+ channels, acetylcholine receptors (nAChRs), and other voltage-gated channels for ions.

  • Excitation-Contraction Coupling:

    • Refers to the process whereby action potential leads to muscle contractions.

    • Involves calcium release from the sarcoplasmic reticulum, leading to muscle fiber contraction.