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Associate Professor W153A Seeley G. Mudd Hall |
Research Interests
We are interested in how and why specific ion channels contribute to 1) rapid information processing in the nervous system, and 2) experience-dependent plasticity in processing and behavior. We have focused on BK (Big calcium-activated K channels) in adrenaline-secreting chromaffin cells of the adrenal gland, where we have described stress- and steroid hormone-related regulation of transcription of the main pore-forming channel gene (Slo) and its Beta subunits, regulation of alternative splicing of Slo, and immediate effects of steroid hormones on channel function. Complementing neuroendocrine and behavioral experiments, we have used a comparative approach, as well, finding robust differences between species, genetic strains, sexes, and developmental stages. To make and test links between gene products and function, we use an eclectic battery of experimental methods, including patch clamp, two-electrode voltage clamp, extracellular recording, quantitative real-time PCR, genetic engineering in mice, and behavioral analysis. For maximal traction, we are now focusing much effort on mice, where several engineered strains give us definitive extremes in which to test the impact of channel regulation and modulation on action potential firing properties of chromaffin cells, and on cardiovascular and behavioral function downstream of adrenaline release. We are very interested in extending what we learn from chromaffin cells to other cells, including pituitary, hippocampus, and other CNS circuitry that participates in stress-responses.
Recent Publications
Chatterjee O., Taylor L. A., Ahmed S., Nagaraj S., Hall J. J., Finckbeiner S. M., Chan P. S., Suda N., King J. T., and McCobb D. P. Social stress alters expression of BK potassium channel subunits in mouse adrenal chromaffin cells. In Revision.
Lai G. J., McCobb D. P. (2006). Regulation of alternative splicing of Slo K+ channels in adrenal and pituitary during the stress-hyporesponsive period of rat development. Endocrinology 147:3961-3967.
King J. T., Lovell P. V., Rishniw M., Kotlikoff M. I., Zeeman M. L., McCobb D. P. (2006). Beta2 and beta4 subunits of BK channels confer differential sensitivity to acute modulation by steroid hormones. J Neurophysiol 95:2878-2888.
McCobb, D. P. (2004). Towards a natural history of calcium-activated potassium channels. In Molecular insights into ion channel biology in health and disease, R. A. Maue, ed. (Amsterdam, Elsevier Science), pp. 51-72.
Mahmoud, S. F., and McCobb, D. P. (2004). Regulation of Slo potassium channel alternative splicing in the pituitary by gonadal testosterone. J Neuroendocrinol 16, 237-243.
Lovell, P. V., King, J. T., and McCobb, D. P. (2004). Acute modulation of adrenal chromaffin cell BK channel gating and cell excitability by glucocorticoids. J Neurophysiol 91, 561-570.
McCobb, D. P., Hara, Y., Lai, G., Mahmoud, S. F., and Flügge, G. (2003). Subordination stress alters alternative splicing of the Slo gene in tree shrew adrenals. Hormones and Behavior 43: 180-186.McCobb, D. P. (2003). Towards a natural history of calcium-activated potassium channels. In: Molecular insights into Ion Channel Biology in Health and Disease, R. Maue, Editor, Elsevier Science, Amsterdam, In Press.
Lai, G. J. and D. P. McCobb (2002). Opposing actions of adrenal androgens and glucocorticoids on alternative splicing of Slo potassium channels in bovine chromaffin cells. Proc Natl Acad Sci U S A 99: 7722-7.
Mahmoud, S.F., Bezzerides, A., Riba R., Lai., G., Lovell, P. V., and McCobb, D. P. (2002). Accurate quantitative RT-PCR for relative expression of Slo splice variants. J Neurosci Methods 115: 189-98.
Lovell, P. V. and McCobb, D. P. (2001). Pituitary Control of BK Potassium Channel Function and Intrinsic Firing Properties of Adrenal Chromaffin Cells. J. Neurosci. 21: 3429-3442.
Courses Taught
Introduction to Neurobiology; Molecular Neurophysiology