Assignment task:
Respond to two of your colleagues 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.
Peer 1: Patience Ndidi Nkwocha
Discussion Week 1-Main Post
Difference between Ion Channels and G-proteins in Signal Transduction and Targets of Medications
Ion channels are integral proteins found in the cell membrane in a process that creates the pathways that allow ion flow. In other words, they form hydrophilic pores across the cell membrane. The said ions include chloride, sodium, calcium, and potassium. These ions and the respective channels support cellular processes, including generating the action potential and releasing neurotransmitters (Pollard et al., 2022). In signal transduction, the ion channels facilitate the opening and closing in response to specific signals, including voltage changes across the cell membrane (Pollard et al., 2022). In the context of medications, it is essential to recognize that treatment modalities that interact with ion channels act by either inhibiting or enhancing ion flows, thus shaping cell activities. Calcium channel blocker(s) is an example of drugs that act by interacting with the ion channels.
G-proteins function as molecular switches inside the cells. They facilitate signal transmission from various stimuli outside a cell to its interior. A conformational change occurs in the receptor when the ligands bind to the G protein-coupled receptors (Liccardo et al., 2020). Once activated, the G protein is further involved in interaction with other molecules to spur a cellular response. Certain medications target the DPCRs to impact the signaling pathways mediated by F-protein.
Mental Illness and Genetic Risk
Having a family history of a particular mental illness elevates one's risk of developing that condition. However, it does not necessarily mean that one will have a mental illness since a positive history does not exclusively count as an illness cause (Firth et al., 2020). A combination of factors, including environmental, lifestyle, and genetics, influence the risk of developing mental illness. It is essential to conduct screening and engage in healthy practices to alleviate preventable risks.
References:
Firth, J., Solmi, M., Wootton, R. E., Vancampfort, D., Schuch, F. B., Hoare, E., ... & Stubbs, B. (2020). A meta-review of "lifestyle psychiatry": the role of exercise, smoking, diet and sleep in the prevention and treatment of mental disorders. World Psychiatry, 19(3), 360-380.
Liccardo, F., Luini, A., & Di Martino, R. (2022). Endomembrane-based signaling by GPCRs and G-proteins. Cells, 11(3), 528, 1-20.
Pollard, T. D., Earnshaw, W. C., Lippincott-Schwartz, J., & Johnson, G. (2022). Cell biology e-book: cell biology e-book. Elsevier Health Sciences.
Peer 2: Jeannette Aldana
Week Assignment:
Explain the difference between ion channels and G proteins as they relate to signal transduction and medication' targets.
Difference between ion channels and G proteins as they relate to signal transduction and targets of medications.
The complex neurological chemical and electrical network requires efficient neuronal communication, requiring intricate coordination between diverse processes (Lovinger et al., 2022). G proteins and ion channel activity are crucial in intracellular communication and neurological functions (Lohse et al., 2024). However, ion channels and G proteins' mechanism of action differ in the reaction speed and proficiency in crossing the cell's "lipid bilayer" (Duncan, 2020, p. 32). On the one hand, ion channels can readily respond to electrical or chemical reactions (Duncan, 2020). G proteins, however, require the mediation of G protein-coupled receptors to receive the regulatory command of the diverse neurotransmitters (Knight et al., 2021). Subsequently, G proteins react with cyclic adenosine monophosphate, "cAMP," contributing to the interlinkage with ion channels (Lohse et al., 2024, p. 387).
Since there is a variety of G protein-coupled receptors and G proteins can also contain different subunits "α, β, and ϒ," their activity and inhibitory or excitatory action are multifaceted because they can either activate or suppress cellular functions (Senese et al., 2018, p. 4). This range of abilities makes "G protein-coupled receptors (CPCRs)" and G proteins excellent targets for specific medication processing (Lohse et al., 2024, P. 387). Ion channels are also divided into different subtypes, namely: "potassium (K) channels, transient receptor potential (TRP) channels, and pentameric ligand-gated ion channels (pLGICs)" (Duncan et al., 2020, p. 32). In the case of continuous stress exposure in rats, Ren et al. (2021) found that their potassium channels were genetically modified to the point of affecting the opening or closure of the potassium ion gates.
The traditional treatment for depression and other psychiatric disorders requires considerable time to achieve therapeutic levels; however, newer medications target specific G protein-coupled receptors directly (Mantas et al., 2022). Consequently, the side effects of CPCRs-based medications will show considerably fewer undesired reactions when compared to traditional treatments (Boczek et al., 2021). Furthermore, promising current studies of using "nanobodies" to target G receptors in the future intend to have even more specificity and rapid therapeutic action while attempting to avoid any unwanted effects (Mantas et al., 2021, p. 541)
How would you answer the following patient question: My grandmother has a mental illness. I have the same genes as her. Will I also get the same mental illness?
According to Cattarinussi et al. (2022), "Major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) share clinical features and genetic bases." (p. 213). However, an adverse immediate environment and continuous negative experiences will make the person susceptible to depressive states (Ren et al., 2021). In the case of depression, a behavioral or stressful environment can certainly alter brain functioning and exacerbate any genetic predispositions (Duman et al., 2019). A study done after exposing rats to sustained stress concluded that "potassium voltage-gated channels" were modified to the point that these changes affected the subjects' genetic level (Ren et al., 2021, p. 173). Furthermore, Kendall et al. (2021) found that statistics of familial depression are as high as "30% and 50%;" however, the development of clinical depression will also depend on environmental factors and exposure to stressors (p. 2226).
References:
Boczek, T., Mackiewicz, J., Sobolczyk, M., Wawrzyniak, J., Lisek, M., Ferenc, B., Guo, F., & Zylinska, L. (2021). The role of G protein-coupled receptors (GPCRs) and calcium signaling in schizophrenia. Focus on GPCRs activated by neurotransmitters and chemokines. Cells, 10(5), 1228.
Cattarinussi, G., Delvecchio, G., Sambataro, F., & Brambilla, P. (2022). The effect of polygenic risk scores for major depressive disorder, bipolar disorder, and schizophrenia on morphological brain measures: a systematic review of the evidence. Journal of Affective Disorders, 310, 213-222.
Duman, R. S., Sanacora, G., & Krystal, J. H. (2019). Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments. Neuron, 102(1), 75-90.
Duncan, A. L., Song, W., & Sansom, M. S. P. (2020). Lipid-dependent regulation of ion channels and G protein-coupled receptors: insights from structures and simulations. Annual Review of Pharmacology & Toxicology, 60, 31-50.
Kendall, K. M., Van Assche, E., Andlauer, T. F. M., Choi, K. W., Luykx, J. J., Schulte, E. C., & Lu, Y. (2021). The genetic basis of major depression. Psychological Medicine, 51(13), 2217-2230.
Knight, K. M., Ghosh, S., Campbell, S. L., Lefevre, T. J., Olsen, R. H. J., Smrcka, A. V., Valentin, N. H., Yin, G., Vaidehi, N., & Dohlman, H. G. (2021). A universal allosteric mechanism for G protein activation. Molecular Cell, 81(7), 1384-1396.
Lohse, M. J., Bock, A., & Zaccolo, M. (2024). G protein-coupled receptor signaling: new insights define cellular nanodomains. Annual Review of Pharmacology & Toxicology, 64, 387-415.
Lovinger, D. M., Mateo, Y., Johnson, K. A., Engi, S. A., Antonazzo, M., & Cheer, J. F. (2022). Local modulation by presynaptic receptors controls neuronal communication and behaviour. Nature Reviews Neuroscience, 23(4), 191-203.
Mantas, I., Saarinen, M., Xu, Z.-Q. D., & Svenningsson, P. (2022). Update on GPCR-based targets for the development of novel antidepressants. Molecular Psychiatry, 27(1), 534-558.
Ren, J., Guo, J., Zhu, S., Wang, Q., Gao, R., Zhao, C., Feng, C., Qin, C., He, Z., Qin, C., Wang, Z., & Zang, L. (2021). The role of potassium channels in chronic stress-induced brain injury. Biological & Pharmaceutical Bulletin, 44(2), 169-180.
Senese, N. B., Rasenick, M & Traynor, J.R., (2018). The Role of G-proteins and g-protein regulating proteins in depressive disorders. Frontiers in Pharmacology, 9.