Kv4 potassium channels regulate action potentials in neurons and cardiac myocytes. Co-expression of EF hand-containing Ca2+-binding proteins termed KChIPs with pore-forming α subunits causes changes the gating amplitude currents (An, W. F., Bowlby, M. R., Betty, M., Cao, J., Ling, H. P., Mendoza, G., Hinson, J. W., Mattsson, K. I., Strassle, B. Trimmer, S., Rhodes, (2000) Nature 403, 553–556). Here we show that profoundly affect intracellular trafficking molecular properties Kv4.2 subunits....

We conducted whole cell voltage-clamp and current-clamp recordings in slices of rat hypothalamus to test for local excitatory synaptic circuits. Local inputs neurons the paraventricular nucleus (PVN) supraoptic (SON) were studied with use electrical chemical stimulation. Extracellular stimulation provided indirect evidence Single stimuli evoked multiple postsynaptic potentials (EPSPs) or currents (EPSCs) some PVN SON cells, invoking polysynaptic inputs. Repetitive (10-20 Hz, 2-10 s) elicited...

Kv4.2 is the primary pore-forming subunit encoding A-type currents in many neurons throughout nervous system, and it also contributes to transient outward of cardiac myocytes. dendrites hippocampal CA1 pyramidal are regulated by activation ERK/MAPK, likely that current. We showed previously directly phosphorylated at three sites ERK/MAPK (T602, T607, S616). In this study we determined whether direct phosphorylation responsible for regulation current observed neurons. made site-directed...

In humans, atrial fibrillation is often triggered by ectopic pacemaking activity in the myocardium sleeves of pulmonary vein (PV) and systemic venous return. However, genetic programs that abnormally reinforce pacemaker properties at these sites how this relates to normal sinoatrial node (SAN) development remain uncharacterized. It was noted previously Nkx2-5, which expressed PV reinforces a chamber-liker myocardial identity PV, lacking SAN. Here we present evidence Shox2 antagonizes...

Calcium-calmodulin-dependent kinase II (CaMKII) has a long history of involvement in synaptic plasticity, yet little focus been given to potassium channels as CaMKII targets despite their importance repolarizing EPSPs and action potentials regulating neuronal membrane excitability. We now show that Kv4.2 acts substrate for vitro have identified phosphorylation sites Ser438 Ser459. To test whether affects channel biophysics, we expressed wild-type or mutant the K(+) interacting protein,...

Schrader, L. A. and J. G. Tasker. Presynaptic modulation by metabotropic glutamate receptors of excitatory inhibitory synaptic inputs to hypothalamic magnocellular neurons. Neurophysiol. 77: 527–536, 1997. The effects activation (mGluRs) on neurons the supraoptic nucleus (SON) were studied with use whole cell patch-clamp microelectrode recordings in acute slices. Application mGluR agonist trans-(±)-1-amino-1,3-cyclopentane dicarboxylic acid ( trans-ACPD, 100 μM) elicited an increase...

Small conductance, Ca²⁺-activated voltage-independent potassium channels (SK channels) are widely expressed in diverse tissues; however, little is known about the molecular regulation of SK channel subunits. Direct alteration ion subunits by kinases a candidate mechanism for functional modulation these channels. We find that activation cyclic AMP-dependent protein kinase (PKA) with forskolin (50 μm) causes dramatic decrease surface localization SK2 subunit COS7 cells due to direct...

A-type channels, encoded by the pore-forming alpha-subunits of Kv4.x family, are particularly important in regulating membrane excitability CNS and heart. Given key role modulation A currents kinases, we sought to investigate protein structure-function relationships underlying regulation these PKA. We have previously shown existence two PKA phosphorylation sites Kv4.2 sequence; therefore, focused this study on primary subunit. In present studies made surprising finding that alpha-subunit is...

Potassium channel interacting proteins (KChIPs) are members of a family calcium binding that interact with Kv4 potassium (K + ) primary subunits and also act as transcription factors. The subunit is K pore-forming subunit, which contributes to the somatic dendritic A-type currents throughout nervous system. These play key role in regulation neuronal excitability processing incoming synaptic information. KChIP3 known calsenilin factor, downstream regulatory element antagonist modulator...

Synaptic excitation and inhibition must be properly balanced in individual neurons neuronal networks to allow proper brain function. Disrupting this balance may lead autism spectral disorders epilepsy. We show the basic helix-loop-helix transcription factor NeuroD2 promotes inhibitory synaptic drive but also decreases cell-intrinsic excitability of cortical pyramidal both vitro vivo. identify two genes potentially downstream NeuroD2-mediated that regulate these parameters: gastrin-releasing...

Non‐technical summary The hippocampus is an area of the brain that important for learning and memory a locus hyperexcitable activity, such as epilepsy. dentate gyrus (DG) controls information flow into rest hippocampus, thus provides protection from excess activity. Under pathological conditions, epilepsy, this protective feature circumvented uninhibited activity flows throughout hippocampus. Activation kappa (κ) opioid receptors (KORs) prevents both behavioural electroencephalographic...

Evidence suggests that when presented with novel acute stress, animals previously exposed to chronic homotypic or heterotypic stressors exhibit normal enhanced hypothalamic-pituitary-adrenal (HPA) response compared solely stressor. The molecular mechanisms involved in this effect remain unknown. extracellular signal-regulated kinase (ERK) is one of the key pathways regulated hippocampus both and stress. aim study was examine interaction prior using variable stress model (CVS), exposure a...

Abstract In aging women, cognitive decline and increased risk of dementia have been associated with the cessation ovarian hormones production at menopause. brain, presence key enzyme aromatase required for synthesis 17‐β‐estradiol (E2) allows local E2 in absence functional ovaries. Understanding how activity is regulated could help alleviate symptoms. female rodents, genetic or pharmacological reduction over extended periods time impair memory formation, decreases spine density, hinders...

Schrader, L. A. and J. G. Tasker. Modulation of multiple potassium currents by metabotropic glutamate receptors in neurons the hypothalamic supraoptic nucleus. Neurophysiol. 78: 3428–3437, 1997. We studied effects activation on intrinsic magnocellular nucleus (SON) with whole cell patch-clamp conventional intracellular recordings coronal slices (400 μm) rat hypothalamus. Trans-(±)-1-amino-1,3-cyclopentane dicarboxylic acid ( trans-ACPD, 10–100 μM), a broad-spectrum receptor agonist, evoked...

Transient outward K+ currents are particularly important for the regulation of membrane excitability neurons and repolarization action potentials in cardiac myocytes. These modulated by PKC (protein kinase C) activation, K+- channel subunit Kv4.2 is a major contributor to these currents. Furthermore, current recorded from channels expressed oocytes reduced activation. The mechanism underlying unknown. In present study, we determined that directly phosphorylates protein. vitro phosphorylation...

Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects odor on signaling cascades associated with long-term remain poorly understood. In this study, we exposed male and female Wistar rats to synthetic 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) assess behavioral physiological responses well rapid modulation signal transduction learning in hippocampus. During exposure...

Memory acquisition and synaptic plasticity are accompanied by changes in the intrinsic excitability of CA1 pyramidal neurons. These activity-dependent mediated modulation currents which alters responsiveness cell to inputs. The afterhyperpolarization (AHP), a major contributor regulation neuronal excitability, is reduced animals that have acquired several types hippocampus-dependent memory tasks also following potentiation high frequency stimulation. BK channels underlie fast AHP contribute...