A researcher is investigating a new antiseizure drug that binds to and activates GABA-A receptors in the central nervous system. During the experiment, she isolates a nerve and uses a microelectrode to measure its membrane potential under physiologic conditions. The resting potential of the nerve is found to be −70 mV. Which of the following membrane potentials will most likely be recorded from this neuron following exposure to the new drug?
Equilibration movements of charged ions under physiologic conditions | ||||
Ion | Charge | Major location | Equilibrium potential | Equilibration movement at -70 mV |
Sodium | Positive | Extracellular | +60 mV | Extracellular gradient drives Na+ into cell, making membrane potential more positive |
Potassium | Positive | Intracellular | -90 mV | Intracellular gradient drives K+ out of cell, making membrane potential more negative |
Chloride | Negative | Extracellular | -75 mV | Extracellular gradient drives Cl- into cell, making membrane potential more negative |
Calcium | Positive | Extracellular | +125 mV | Extracellular gradient drives Ca2+ into cell, making membrane potential more positive |
The GABA-A receptor is an ionotropic receptor (eg, part of an ion channel) that regulates the flow of negatively charged chloride ions across the neuronal cell membrane. A drug that binds to and activates GABA-A receptors will increase the conductance of chloride ions, causing passive transport down the concentration gradient into the cell interior. This causes the membrane potential to become hyperpolarized (more negative than the resting membrane potential) by approaching or reaching the equilibrium potential for chloride (−75 mV). A cell that becomes hyperpolarized is temporarily made refractory to firing an action potential.
(Choice B) Exposure to the experimental drug will make the neuronal membrane potential more negative than the resting membrane potential due to the opening of chloride channels.
(Choice C) The opening of ligand-gated (controlled by binding of neurotransmitters) sodium channels allows for the initial influx of positively charged sodium ions. This causes a graded depolarization of the neuronal cell membrane toward the threshold for firing an action potential (−55 mV).
(Choices D, E, F, and G) Once the threshold membrane potential is reached, fast voltage-gated sodium channels open to mediate the upstroke phase of the neuronal action potential. During this time, the membrane potential becomes even more positive due to the rapid influx of sodium ions and causes the membrane potential to approach the equilibrium potential for sodium (+60 mV).
(Choice H) The influx of positively charged calcium ions can raise the membrane potential even further (more positive than +60 mV) toward the equilibrium potential for calcium ions (+125 mV).
Educational objective:
A drug that binds to and activates GABA-A receptors (or enhances their activity) will increase the conductance of chloride ions, leading to increased passive transport of chloride into the cell interior. This causes the membrane potential to become hyperpolarized (more negative than the resting membrane potential) by approaching or reaching the equilibrium potential for chloride.