Cell Type Specific Spatial and Functional Coupling Between Mammalian Brain Kv2.1 K+ Channels and Ryanodine Receptors

Download or read book Cell Type Specific Spatial and Functional Coupling Between Mammalian Brain Kv2.1 K+ Channels and Ryanodine Receptors written by Danielle Nicole Mandikian and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Communication between neurons is a result of complex signaling networks. At the heart of this vast network is an intricate repertoire of ion channels whose activity give rise to directed cellular function. In order for these signaling events to occur, ion channels must be trafficked to the correct subcellular domains and function properly once there. A major mechanism to regulate this is through dynamic post translational modifications and the formation of multi protein complexes that regulate the microenvironments in which these proteins function. Voltage gated potassium channels (Kv channels) are crucial molecules that control electrical signaling by establishing membrane resting potential, frequency and duration of action potentials as well as control the release of neurotransmitters. The diversity observed in these channels are attributable to the subunits expressed as well as post-translational modifications and signaling complexes which characteristically modulate function. One broadly expressed subunit, Kv2.1, has been found to be expressed in many neuron classes throughout the brain. Kv2.1 has been shown to play a key role in homeostatic regulation of neuronal intrinsic excitability in multiple neuron classes. Phosphorylation at more than 30 sites on the c-terminus of Kv2.1 have been shown to regulate localization as well as activation of the channel. Recently Kv2.1 has also been shown to be SUMOylated, resulting in similar functional consequence as phosphorylation. To date, little is known about the complete network of Kv2.1 modifications in terms of cross talk, as well as molecular complexes that form with Kv2.1 throughout the brain which might regulate this. In Chapter 1, I introduce Kv2.1 and what is known about mechanisms which regulate its activity, In Chapter 2, I review the role of phosphorylation and SUMOylation in the regulation of Kv2.1 activity. In Chapter 3, I present unpublished work detailing the spatial and functional coupling between mammalian brain Kv2.1 and Ryanodine Receptors in a cell type specific manner. In Chapter 4, I discuss questions that arise about the nature and functional consequences of the association between Kv2.1 and RyR.