Respond by supporting or expanding on their explanation, as well as how they have described their response to the patient. Peer responses should include at least two (2) supporting scholarly, peer-reviewed references outside of the provided Learning Resources. Your responses should also include additional resources to either support or refute the responses and should demonstrate critical thinking.

Note: Be sure you work to share additional perspectives on the details described by your colleague. Responses of “I agree” or “good point” will result in lower score grading.

Discussion 1

Location: G proteins are found inside cells and function as bridges in signaling pathways, while ion channels are embedded in the cell membrane and directly control ion flow being more selective.

Mechanism: G proteins activate downstream signaling events following GPCR activation, while ion channels directly regulate ion passage. Many ion channels, including most Na, K, Ca, and some Cl channels, are gated by voltage; however, some ion channels, including TRP channels, ryanodine receptors, IP3 receptors, and some K and Cl channels, are relatively voltage-insensitive and are gated by second messengers and other intracellular and extracellular mediators. (Alexander et al., 2021b). GPCRs, or G protein-coupled receptors, couple to heterotrimeric G proteins belonging to the Gi/o, Gq, Gs, and G12/13 classes to convert extracellular stimuli into intracellular signaling (Masuho et al., 2023).  

Targets: Ion channel-specific drugs influence ion flow directly, while G protein-specific drugs modulate signaling pathways. Ion channel-targeting medications have a long history of being used as local anesthetics as well as essential therapeutics for a variety of critical indications, such as cardiovascular disorders like angina, hypertension, and cardiac arrhythmias; metabolic disorders like type II diabetes; and neurological disorders like pain and stroke (Team, 2020). G protein-coupled receptors (GPCRs) account for approximately 35% of all FDA-approved drugs. Of the GPCRs, many are orphaned, meaning they have no known endogenous ligand; this presents a challenging but unexplored area for finding new therapeutic targets. G protein-coupled receptor 37 (GPR37) is one of the more well-known orphan GPCRs (oGPCRs). It is highly expressed in the central nervous system (CNS), especially in the spinal cord and oligodendrocytes (Bolinger et al., 2023).  

Exploring the Genetic Links to Mental Illness: Will I Inherit My Grandmother’s Condition?

      While genetics can increase susceptibility to certain mental illnesses, it’s not a definitive predictor. Individual experiences, lifestyle choices, environment, and general health also play significant roles. So, no, you may not necessarily develop the same condition as your grandmother. Research conducted and funded by the National Institute of Mental Health (NIMH) has found that many mental disorders are caused by a combination of biological, environmental, psychological, and genetic factors. In fact, a growing body of research has found that certain genes and gene variations are associated with mental disorders.

Discussion 2

Difference Between Ion Channels and G Proteins

Ion channels and G proteins play an important part in physiological and pathological processes in the body and in targeting medications, but both go about it differently. Natural ion channels are “composed of large proteins that form pores spanning through the lipid membrane, and they can be grouped based on ion selectivity” and function via different gating mechanisms – activation mediated by voltage, ligand, mechanical, or light stimulation (Picci et al., 2022, para 1). FDA-approved medications can treat many diseases via blocking ion channels, such as calcium channel blockers, which are utilized for populations suffering from hypertension, Alzheimer’s disease, depression, and other psychiatric disorders (Picci et al., 2022, para 3).

            G proteins, or G protein-coupled receptors (GPCRs), are considered the largest protein family in the human genome; these proteins are located on the cell membrane and “transduce extracellular signals [photons, ions, proteins, neurotransmitters, and hormones] into key physiological effects” (Yang et al., 2021, para 1). GPCRs, specifically Class A/rhodopsin family, are the most targeted therapeutically in terms of medication as it has a wide range of functions with indications for “analgesics, allergies, cardiovascular diseases, hypertension, pulmonary diseases, depression, migraine, glaucoma, Parkinson’s disease, schizophrenia, cancer-related fatigue,” and many more diseases and related issues (Yang et al., 2021, para 5).

Genetic Predisposition to Mental Illness

If I were to have a patient approach me inquiring if they are genetically predisposed to mental illness, I would answer in the affirmative with a few caveats. It has always been speculated that mental illness comes either from nature or nurture, but it is much more complex than that. It has been shown within twin, adoption, family, and population-based studies that “all major psychiatric disorders have a substantial heritability.” Still, environmental exposures also influence the risk factors of mental illness (Andreassen et al., 2023, para 9). The likelihood of inheriting a psychiatric disorder depends on what the disorder is classified – psychotic and neurodevelopmental disorders (74-85%), while those with mood and anxiety disorders (37-58%) are less likely to inherit the disorders and are more in relation to environmental factors (Andreassen et al., 2023, para 10). Yet, both can overlap with one another, showing it is not nature versus nurture but both intertwined. Therefore, I would ask the patient what mental illness their grandmother suffers from, and with the knowledge above, explain their likely risk of obtaining that specific mental illness.