Dr. Michelle Mynlieff

Dr. Michelle Mynlieff
Dr. Michelle MynlieffMarquette University

Wehr Life Sciences, 508A

MilwaukeeWI53201United States of America
(414) 288-1467

Professor, Chair

Ion channels and neuronal function

Publications

Education

B.A. 1983, Cornell University, Ithaca, NY
Ph.D. 1988, University of Colorado Health Sciences Center
Postdoctoral Fellow, Colorado State University, Bolder, CO

Research Interests

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 (CaV2.2) and facilitates L-type calcium current (CaV1.2, and/or 1.3) by activation of GABABreceptors 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  K+Cl- co-transporter (KCC2) expression in hippocampal neurons.  We have demonstrated that this increase in KCC2 expression is dependent on influx of calcium through L-type channels giving support for a role of L-type calcium channels in regulating gene expression during development.  We have been investigating the different components of the signaling pathway leading to the enhancement of l-type current.  The enhancement of L-type calcium current in neonatal hippocampus requires activation of protein kinase C and not calmodulin-calcium dependent kinase II.  Immunocytochemical experiments have determined that PKCα is translocated to the membrane by GABAB receptor activation.  Neurons that have their Gq type of G-protein knocked down with morpholinos in culture no longer demonstrate the enhancement of L-type current with GABAB receptor activation.  A combination of whole cell patch clamp recording and ratiometric calcium imaging in acutely dissociated hippocampal neurons is being utilized to isolate various components of the pathway pharmacologically or through knockdown experiments.  Western blot analysis and confocal imaging has been utilized to study the developmental expression of the L-type calcium channel isoforms and co-localization of the channels with GABAB receptors.

Students

Michael Hunsburger (Ph.D. student)

Dr. Mynlieff is currently accepting new Ph.D. students into her lab

 

Former Students and Postdoctoral Fellows

Jennifer R. Carter, 2001, M.S.
Thomas J. Carter, 2002, Ph.D.
Robert L. Keesey, Ph.D., postdoctoral fellow
Jennifer G. Bray, 2010, Ph.D.
Andrew S. Karls, 2014, Ph.D.

 


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Department of Biological Sciences

Wehr Life Sciences, 109
1428 W. Clybourn St.
Milwaukee, WI 53233

(414) 288-7355

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