Kv2.1 Potassium Channels Regulate Repetitive Burst Firing in Extratelencephalic Neocortical Pyramidal Neurons.

Coincidence detection and cortical rhythmicity are both greatly influenced by neurons' propensity to fire bursts of action potentials. In the neocortex, repetitive burst firing can also initiate abnormal neocortical rhythmicity (including epilepsy). Bursts are generated by inward currents that underlie a fast afterdepolarization (fADP) but less is known about outward currents that regulate bursting.

PIP alters of Ca currents in acutely dissociated supraoptic oxytocin neurons.

Magnocellular neurosecretory cells (MNCs) occupying the supraoptic nucleus (SON) contain voltage-gated Ca channels that provide Ca for triggering vesicle release, initiating signaling pathways, and activating channels, such as the potassium channels underlying the afterhyperpolarization (AHP). Phosphotidylinositol 4,5-bisphosphate (PIP ) is a phospholipid membrane component that has been previously shown to modulate Ca channels, including in the SON in our previous work. In this study, we further investigated the ways in which PIP modulates these channels, and for the first time show how PIP modulates Ca channel currents in native membranes.

Functional roles of Kv1-mediated currents in genetically identified subtypes of pyramidal neurons in layer 5 of mouse somatosensory cortex.

We used voltage-clamp recordings from somatic outside-out macropatches to determine the amplitude and biophysical properties of putative Kv1-mediated currents in layer 5 pyramidal neurons (PNs) from mice expressing EGFP under the control of promoters for etv1 or glt. We then used whole cell current-clamp recordings and Kv1-specific peptide blockers to test the hypothesis that Kv1 channels differentially regulate action potential (AP) voltage threshold, repolarization rate, and width as well as rheobase and repetitive firing in these two PN types. We found that Kv1-mediated currents make up a similar percentage of whole cell K current in both cell types, and only minor biophysical differences were observed between PN types or between currents sensitive to different Kv1 blockers.

Roles of specific Kv channel types in repolarization of the action potential in genetically identified subclasses of pyramidal neurons in mouse neocortex.

The action potential (AP) is a fundamental feature of excitable cells that serves as the basis for long-distance signaling in the nervous system. There is considerable diversity in the appearance of APs and the underlying repolarization mechanisms in different neuronal types (reviewed in Bean BP. Nat Rev Neurosci 8: 451-465, 2007), including among pyramidal cell subtypes.

Distinct Cell- and Layer-Specific Expression Patterns and Independent Regulation of Kv2 Channel Subtypes in Cortical Pyramidal Neurons.

Unlabelled: The Kv2 family of voltage-gated potassium channel α subunits, comprising Kv2.1 and Kv2.2, mediate the bulk of the neuronal delayed rectifier K(+) current in many mammalian central neurons.

Electrophysiological properties of genetically identified subtypes of layer 5 neocortical pyramidal neurons: Ca²⁺ dependence and differential modulation by norepinephrine.

We studied neocortical pyramidal neurons from two lines of bacterial artificial chromosome mice (etv1 and glt; Gene Expression Nervous System Atlas: GENSAT project), each of which expresses enhanced green fluorescent protein (EGFP) in a different subpopulation of layer 5 pyramidal neurons. In barrel cortex, etv1 and glt pyramidal cells were previously reported to differ in terms of their laminar distribution, morphology, thalamic inputs, cellular targets, and receptive field size. In this study, we measured the laminar distribution of etv1 and glt cells.

Kv2 channels regulate firing rate in pyramidal neurons from rat sensorimotor cortex.

The largest outward potassium current in the soma of neocortical pyramidal neurons is due to channels containing Kv2.1 α subunits. These channels have been implicated in cellular responses to seizures and ischaemia, mechanisms for intrinsic plasticity and cell death, and responsiveness to anaesthetic agents.

Whole cell recording from an organotypic slice preparation of neocortex.

We have been studying the expression and functional roles of voltage-gated potassium channels in pyramidal neurons from rat neocortex. Because of the lack of specific pharmacological agents for these channels, we have taken a genetic approach to manipulating channel expression. We use an organotypic culture preparation (16) in order to maintain cell morphology and the laminar pattern of cortex.

Postnatal development of A-type and Kv1- and Kv2-mediated potassium channel currents in neocortical pyramidal neurons.

Potassium channels regulate numerous aspects of neuronal excitability, and several voltage-gated K(+) channel subunits have been identified in pyramidal neurons of rat neocortex. Previous studies have either considered the development of outward current as a whole or divided currents into transient, A-type and persistent, delayed rectifier components but did not differentiate between current components defined by α-subunit type. To facilitate comparisons of studies reporting K(+) currents from animals of different ages and to understand the functional roles of specific current components, we characterized the postnatal development of identified Kv channel-mediated currents in pyramidal neurons from layers II/III from rat somatosensory cortex.

Experimental evidence of improved transthoracic defibrillation with electroporation-enhancing pulses.

Unlabelled: There is considerable work on defibrillation wave form optimization. This paper determines the impedance changes during defibrillation, then uses that information to derive the optimum defibrillation wave form.

Methods Part I: Twelve guinea pigs and six swine were used to measure the current wave form for square voltage pulses of a strength which would defibrillate about 50% of the time.

Experimental verification of theoretical predictions concerning the optimum defibrillation waveform.

The efficacy of electrical therapy at terminating ventricular fibrillation is highly dependent on the waveform used. We present experimental results which test one theory for defibrillation waveform dependence. Forty-four defibrillation waveforms (22 monophasic, 22 biphasic) were designed according to the theoretical construct of Fishier (2000).

Analysis of the defibrillation efficacy for 5-ms waveforms.

Introduction: Empirical studies have shown that biphasic defibrillation waveforms are more efficacious than monophasic waveforms. However, a more systematic approach to waveform development might be more productive. This study tested 147 multiphasic waveforms uniformly sampled from all possible 5-ms waveforms.

The defibrillation efficacy of high frequency alternating current sinusoidal waveforms in guinea pigs.

There have been few basic studies of alternating current (AC) defibrillation, despite growing interest in the ability of AC to terminate or alter ongoing fibrillation. Based on fibrillation threshold testing, it has been suggested that cardiac tissue is most sensitive to long duration, low strength AC stimulation at around 50 Hz. This has not been directly tested for defibrillation.