Voltage-gated potassium currents play a crucial role in controlling neuronal excitability and sculpting patterns of neuronal activity. Consistent with these roles, K+ channels are exceptionally diverse. This diversity comes in part, from multiple genes, post-translational mechanisms, and heteromeric co-assembly of subunits. Recent molecular work has documented the diversity of subunits and has revealed some of the rules governing the association of subunit types. Studies in expression systems have demonstrated the biophysical and pharmacological properties of defined channel types. Relatively little is known about the composition of K+ channels in native membranes. The division of labor between the various K+ channel types in individual cells is also incompletely understood. Firing of regular-spiking (RS) pyramidal neurons in neocortex is characterized by relatively broad spikes, modest fAHPs, complex subthreshold integration, and rhythmic, repetitive firing with spike-frequency adaptation (SFA). In vivo studies indicate that the characteristic firing pattern of RS cells is integral to their functions in local circuit processing. Previous work by others and ourselves indicate that neocortical pyramidal cells express several K+ currents which regulate excitability. In particular, there is a diversity of slowly inactivating currents. This proposal is to (1) characterize the slowly-inactivating voltage-gated K+ currents and channel subunits in layer II/III pyramidal neurons from rat somatosensory cortex, (2) determine the relationship between particular channel subunits and macroscopic K+ currents, and (3) determine the mechanisms by which voltage-gated K+ currents regulate the RS firing pattern. These data are essential for understanding how pyramidal cells integrate synaptic inputs into spike trains, a process underlying cortical output. This work will also provide insights into abnormal cortical excitability and disease processes, such as epilepsy, as well as provide knowledge of the substrate for modulation by transmitters.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS044163-04
Application #
7020639
Study Section
Molecular, Cellular and Developmental Neurosciences 2 (MDCN)
Program Officer
Silberberg, Shai D
Project Start
2003-03-01
Project End
2008-06-30
Budget Start
2006-03-01
Budget End
2008-06-30
Support Year
4
Fiscal Year
2006
Total Cost
$302,394
Indirect Cost
Name
University of Tennessee Health Science Center
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
941884009
City
Memphis
State
TN
Country
United States
Zip Code
38163
Wang, Lie; Chandaka, Giri Kumar; Foehring, Robert C et al. (2018) Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy. J Neurophysiol 119:1745-1752
Baker, Arielle; Kalmbach, Brian; Morishima, Mieko et al. (2018) Specialized Subpopulations of Deep-Layer Pyramidal Neurons in the Neocortex: Bridging Cellular Properties to Functional Consequences. J Neurosci 38:5441-5455
Guan, Dongxu; Pathak, Dhruba; Foehring, Robert C (2018) Functional roles of Kv1-mediated currents in genetically identified subtypes of pyramidal neurons in layer 5 of mouse somatosensory cortex. J Neurophysiol 120:394-408
Kirchner, Matthew K; Foehring, Robert C; Callaway, Joseph et al. (2018) Specificity in the interaction of high-voltage-activated Ca2+ channel types with Ca2+-dependent afterhyperpolarizations in magnocellular supraoptic neurons. J Neurophysiol 120:1728-1739
Kirchner, Matthew K; Foehring, Robert C; Wang, Lie et al. (2017) Phosphatidylinositol 4,5-bisphosphate (PIP2 ) modulates afterhyperpolarizations in oxytocin neurons of the supraoptic nucleus. J Physiol 595:4927-4946
Pathak, Dhruba; Guan, Dongxu; Foehring, Robert C (2016) Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex. J Neurophysiol 115:2317-29
Bishop, Hannah I; Guan, Dongxu; Bocksteins, Elke et al. (2015) Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons. J Neurosci 35:14922-42
Guan, Dongxu; Armstrong, William E; Foehring, Robert C (2015) Electrophysiological properties of genetically identified subtypes of layer 5 neocortical pyramidal neurons: Ca²? dependence and differential modulation by norepinephrine. J Neurophysiol 113:2014-32
Guan, Dongxu; Armstrong, William E; Foehring, Robert C (2013) Kv2 channels regulate firing rate in pyramidal neurons from rat sensorimotor cortex. J Physiol 591:4807-25
Andrade, Rodrigo; Foehring, Robert C; Tzingounis, Anastasios V (2012) The calcium-activated slow AHP: cutting through the Gordian knot. Front Cell Neurosci 6:47

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