B.A. 1983, Cornell University
Ph.D. 1988, University of Colorado Health Sciences Center
Postdoctoral Fellow, Colorado State University
Ion Channels and Neuronal Function
Intracellular 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.
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 and this effect peaks in the first postnatal week. This facilitation coincides with the developmental up-regulation of potassium coupled chloride transporter levels in the hippocampal neurons. We have demonstrated that this increase in protein levels is dependent on influx of calcium through L-type channels giving support for a role of L-type calcium channels in regulating gene expression. Current studies are underway to elucidate the signal transduction mechanisms. The laboratory uses a combination of techniques in these studies including whole cell patch clamp recording in acutely dissociated hippocampal neurons and hippocampal slices, ratiometric calcium imaging, immunohistochemistry, and Western blot analysis.
Selected Publications
J.G. Bray and M. Mynlieff. Influx of calcium through L-type calcium channels is necessary for the early postnatal upregulation of the potassium-coupled chloride transporter KCC2 in the rat hippocampus, in preparation, 2009.
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. Neuroscience. 93(2):979-986.
Abstracts from Meetings 2008-10
J.G. Bray and M. Mynlieff. 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 M. Mynlieff. Modulation of chloride transporter expression in early postnatal rat hippocampus by calcium influx through L-type calcium channels. Society for Neuroscience, 34, 2008.
A.S. Karls, E.R. Weh, and M. Mynlieff. Modulation of intracellular calcium in neonatal hippocampus by GABAB receptors. Society for Neuroscience, 35, 2009.
J.G. Bray and M. Mynlieff. Signal transduction mechanism of L-type calcium current facilitation by GABA-B receptor activation in the neonatal rat hippocampus. Society for Neuroscience, 35, 2009.
Current Students
- Jennifer G. Bray, Ph.D. Candidate
- Andrew S. Karls, Ph.D. Candidate
Former Students and Postdoctoral Fellows
- Jennifer R. Carter, M.S., 2001
- Thomas J. Carter, Ph.D., 2002
- Robert L. Keesey, Ph.D., postdoctoral fellow
Biological Sciences Department
Marquette University, Wehr Life Sciences
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P.O. Box 1881
Milwaukee, WI 53201-1881
(414) 288-7355
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