Angela R. Cantrell, Ph.D.
Department of Anatomy and Neurobiology
The University of Tennessee
Health Science Center
The University of Tennessee Health Science Center
855 Monroe Avenue, Suite 515
Memphis, TN 38163
Phone: (901) 448-1534
Fax: (901) 448-7193
Lab: 416 Wittenborg Anatomy Building
Email: Angela R. Cantrell
- Ph.D. Institution: Department of Anatomy and Neurobiology, UTHSC, Memphis, TN
- Postdoctoral: Department of Pharmacology, University of Washington, Seattle, WA
The electrical signals that are required for neural transmission are mediated by the flow of ions across the neuronal membrane via a class of proteins called ion channels. These channel proteins form pores in the neuronal membrane for the regulated passage of selected ion species. The properties of these channels determine neuronal excitability and dictate action potential firing and subsequent neurotransmitter release. Ion channel activity is tightly regulated through the activation of membrane associated or cytoplasmic second messenger signaling cascades. This regulatory influence plays an important role in the normal functioning of the central nervous system (CNS).
Neurotransmitters are common mediators of second messenger activity in the CNS and often target particular classes of ion channels. Our previous electrophysiological studies have revealed the modulatory effects of a number of neurotransmitters on calcium and sodium conductances in the striatum, cortex and hippocampus. Recent studies on the modulatory action of neurotransmitters in the CNS indicate that different classes of neurotransmitter receptors may activate multiple intracellular signaling cascades may converge upon a single class of ion channels. This type of convergence provides the central nervous system with the ability to "fine tune" the response of a neuron to a particular stimulus by regulating its firing behavior.
Interestingly, alterations in neurotransmitter function and second messenger activation are commonly observed in a number of neurodegenerative disorders including Huntington's disease, Alzheimer's disease and Parkinson's disease. We hypothesize that ion channel activity may be altered in response to the loss of normal regulatory mechanisms. This may result in impairments in the ability of the neuron to precisely control it's response to incoming stimuli and may underlie neuronal dysfunction in the diseased state.
My laboratory uses a multidisciplinary approach to test the hypothesis that alterations in the localization, physiological properties and regulation of voltage-gated ion channels occur in neurodegenerative disorders and may play a role mediating neuronal dysfunction that ultimately gives rise to neuronal death. We employ voltage-clamp electrophysiological techniques, molecular biology, protein biochemistry, immunocytochemistry and confocal microscopy to test this hypothesis using transgenic and cellular models of neurodegenerative diseases. It is our hope that these experiments will lead to exciting discoveries about the mechanisms underlying the devastating symptoms of these diseases and help to pinpoint more efficient strategies for the treatment of neurodegenerative disorders.
- Foehring RC, Guan D, Toleman T, Cantrell AR. Whole cell recording from an organotypic slice preparation of neocortex. J Vis Exp. 2011 Jun 3;(52). pii: 2600. doi: 10.3791/2600. PubMed PMID: 21673642; PubMed Central PMCID: PMC3197031.
- Cook DG, Li X, Cherry SD, Cantrell AR. Presenilin 1 deficiency alters the activity of voltage-gated Ca2+ channels in cultured cortical neurons. J Neurophysiol. 2005 Dec;94(6):4421-9. Epub 2005 Sep 7. PubMed PMID: 16148264.
- Chen Y, Cantrell AR, Messing RO, Scheuer T, Catterall WA. Specific modulation of Na+ channels in hippocampal neurons by protein kinase C epsilon. J Neurosci. 2005 Jan 12;25(2):507-13. PubMed PMID: 15647496.
- Carr DB, Day M, Cantrell AR, Held J, Scheuer T, Catterall WA, Surmeier DJ. Transmitter modulation of slow, activity-dependent alterations in sodium channel availability endows neurons with a novel form of cellular plasticity. Neuron. 2003 Aug 28;39(5):793-806. PubMed PMID: 12948446.
- Cantrell AR, Tibbs VC, Yu FH, Murphy BJ, Sharp EM, Qu Y, Catterall WA, Scheuer T. Molecular mechanism of convergent regulation of brain Na(+) channels by protein kinase C and protein kinase A anchored to AKAP-15. Mol Cell Neurosci. 2002 Sep;21(1):63-80. PubMed PMID: 12359152.
- Cantrell AR, Catterall WA. Neuromodulation of Na+ channels: an unexpected form of cellular plasticity. Nat Rev Neurosci. 2001 Jun;2(6):397-407. Review. PubMed PMID: 11389473.