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MICHELLE MYNLIEFF
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Ion Channels and Neuronal FunctionIntracellular calcium concentration is crucial in controlling many aspects of neuronal function including regulation of neurotransmitter release and activation/inactivation of various genes and enzymes. One of the main sources of increasing calcium concentration is by influx through calcium channels that open in response to changes in voltage (voltage dependent calcium channels). Thus, modulation of calcium channels is a prime mechanism by which neurotransmitters can regulate neuronal function. The main interest in my laboratory is in the modulation of these channels. More specifically, the current research program is investigating the mechanisms and functional significance of GABAB receptor modulation of voltage dependent calcium channels in the hippocampal brain region. GABA (γ-aminobutyric acid) is the main inhibitory neurotransmitter in the mammalian brain. Pharmaceutical compounds that interact with receptors for GABA such as barbiturates and valium, are routinely prescribed for anxiety, epilepsy, insomnia, etc. Unfortunately, these types of pharmaceutical compounds interact with most inhibitory synapses making side effects, such as drowsiness, fatigue, mental slowing, and double vision common. By increasing our understanding of the specific effects of GABA, it will be possible to design better pharmaceutical agents for a particular disorder. Previous studies in our laboratory have demonstrated that GABA attenuates N-type calcium current (Cav 2.2) and facilitates L-type calcium current (Cav 1.1, 1.2, and/or 1.3) by activation of GABAB receptors in the early neonatal period in the superior region of rat hippocampus. The facilitation of L-type current is a novel finding not previously demonstrated in the mammalian central nervous system. Current studies are underway to elucidate the signal transduction mechanisms and functional significance of these opposing effects of GABAB receptor activation. In addition, we are investigating the potential role of L-type calcium current facilitation in the early postnatal period on expression levels of chloride transporters, which are known to undergo changes in the first few postnatal weeks. The laboratory uses a combination of techniques in these studies including whole cell patch clamp recording in acutely dissociated hippocampal neurons and hippocampal slices as well as immunohistochemistry and Western blot analysis.
C.L. Stuckey, McGinley, E., Chernoff, D.I., and Mynlieff, M. 2007. Nerve injury-induced increase in cold responses are independent of TRPM8 or TRPA1. In preparation. Carter, T.J. and Mynlieff, M. 2004. GABAB receptors facilitate L-type and attenuate N-type Ca2+ currents in isolated hippocampal neurons. Journal of Neuroscience Research, 76(3), 323-33. Carter, J.R. and M. Mynlieff. 2003. Amyotrophic lateral sclerosis patient IgG alters voltage-dependence of Ca2+ channels in dissociated rat motoneurons. Neuroscience Letters, 353(3), 221-5. McCallum, J.B., Kwok, W.-M., Mynlieff, M., Bosnjak, B., and Hogan, Q.H. 2003. Loss of T-type calcium current in sensory neurons of rats with neuropathic pain. Anesthesiology, 98, 209-16, 2003. Mynlieff, M. 1999. Identification of interneuronal subtypes in cultures obtained from postnatal hippocampus using electrophysiological parameters. Neurosci. 93(2):979-986.
Abstracts from Meetings 2008-09 J.G. Bray and Mynlieff, M. L-type calcium current facilitation by GABAB receptor activation peaks at postnatal day 7 in the rat hippocampus. Society for Neuroscience, 34, 2008.
M.M. Marcetich*, J.G. Bray and Mynlieff, M. Modulation of chloride transporter expression in early postnatal rat hippocampus by calcium influx through L-type calcium channels. Society for Neuroscience, 34, 2008. Current Students
Former Students and Postdoctoral Fellows
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