Molecular and cellular physiology of epilepsy-associated genes.
Our interest is to reveal the mechanisms by which epilepsy-associated molecules and signaling networks lead to epileptogenesis in the neonatal and infantile brain. In the current genomic era, gene mutations are identified in pediatric patients with increasing frequency, but it is unclear how the myriad of identified proteins and signaling networks are organized to regulate neuronal excitability. Our lab addresses this question using a multidisciplinary approach that combines electrophysiology, pharmacology and microscopy in genetically modified mice lines. Much of our work has dissected the cell-type and brain-region specific effects that epilepsy-associated potassium channel genes have on neuronal physiology. Such knowledge is critical for the development of new anticonvulsant molecules that have a more targeted action in the brain. Going forward, we will continue to study the role of epilepsy-associated genes, expanding our research into the mechanisms underlying the seizures triggered by recently identified mutations in non-ion channel genes.
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Tzingounis AV. SMITten for KCNQ Channels. Biophys J. 2017 Aug 8;133(3):503-505.
Zhang Y, Abiraman K, Li H, Pierce DM, Tzingounis AV, Lykotrafitis G. Modeling of the axon membrane skeleton structure and implications for its mechanical properties. PLoS Comput Biol. 2017 Feb 27; 13(2):e1005407.
Niday Z, Hawkins VE, Soh H, Mulkey DK, Tzingounis AV. Epilepsy-Associated KCNQ2 Channels Regulate Multiple Intrinsic Properties of Layer 2/3 Pyramidal Neurons. J Neurosci. 2017 Jan 18;37(3):576-586.
Abiraman K, Sah M, Walikonis RS, Lykotrafitis G, Tzingounis AV. Tonic PKA Activity Regulates SK Channel Nanoclustering and Somatodendritic Distribution. J Mol Biol. 2016 Jun 5;428(11):2521-37.
Kim KS, Duignan KM, Hawryluk JM, Soh H, Tzingounis AV. The Voltage Activation of Cortical KCNQ Channels Depends on Global PIP2 Levels. Biophys J. 2016 Mar 8;110(5):1089-98.
Kalappa BI, Soh H, Duignan K, Furuya T, Edwards S, Tzingounis AV*, Tzounopoulos T*. Novel Kv7.2/3 (KCNQ2/3)-specific channel activator suppresses in vivo epileptic activity and prevents the development of tinnitus. JNeurosci. 35(23):5311-21 (2015) . *co-corresponding authors
Mulkey DK, Hawkins VE, Hawryluk JM, Takakura AC, Moreira TS, Tzingounis AV. Molecular underpinning of ventral surface chemoreceptor function: focus on KCNQ channels. J Physiol. 2015 Mar 1;593(5):1075-1081.
Hawkins VE, Hawryluk JM, Takakura AC, Tzingounis AV, Moreira TS, Mulkey DK. HCN Channels contribute to serotonergic modulation of ventral surface chemosensitive neurons and respiratory activity. J Neurophysiol. 2015 Feb 15;113(4):1195-205.