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An electrophysiologist is performing intracellular recordings on neuronal cells in culture. He is trying to identify a drug that would reliably increase the firing rate in the cultured cells. Assuming the cells in question express all of the following receptor types, an agonist at which of the following receptors would most likely produce an increase in firing rate?
A. Alpha-2 adrenergic
B. Beta-1 adrenergic
C. Gamma-aminobutyric acid
D. Glycine
E. N-methyl-D-aspartate
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GREATTTTTT
The correct answer is E. The answer options contain a mix of ligand-gated ion channel receptors and G protein coupled receptors. A receptor that would reliably produce excitation, thus increasing in firing rate, would be an excitatory amino acid receptor. The N-methyl-D-aspartate (NMDA) receptor is an example of this type of receptor. The NMDA receptor is a ligand-gated ion channel that would permit the influx of cations (sodium and calcium). The rule of thumb is that cations entering the cell through ion channels produce depolarization, and anions entering the cell cause hyperpolarization.
The alpha-2 adrenergic receptor (choice A) is coupled to Gi, and would lead to a decrease in cAMP levels.
The beta-1 adrenergic receptor (choice B) is coupled to Gs, and would lead to an increase in cAMP levels.
The gamma-aminobutyric acid (GABA) (choice C) and glycine (choice D) receptors are inhibitory amino acid receptors. They are ligand-gated ion channel receptors that allow chloride influx. This could cause hyperpolarization, or at least membrane potential stabilization, thus preventing excitation of the cell.
