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Alon Korngreen

Publications and source records attributed to Alon Korngreen.

10 recordsLinked to original sources
PubMed2006

Dendritic voltage-gated K+ conductance gradient in pyramidal neurones of neocortical layer 5B from rats.

Voltage-gated potassium channels effectively regulate dendritic excitability in neurones. It has been suggested that in the distal apical dendrite of layer 5B (L5B) neocortical pyramidal neurones, K+ conductances participate in active dendritic synaptic integration and control regenerative dendritic potentials. The ionic mechanism for triggering these regenerative potentials has yet to be elucidated. Here we used two-electrode voltage clamp (TEVC) to quantitatively record K+ conductance densities of a sustained K+ conductance in the soma and apical dendrite of L5B neurones of adult rats. We report that the somatic and proximal dendritic sustained voltage-gated K+ conductance density is more than 10-fold larger than previous estimates. The results obtained using TEVC were corroborated using current-clamp experiments in combination with compartmental modelling. Possible error sources, including inaccurate measurement of the passive membrane parameters and unknown axonal and basal dendritic conductance distributions, were shown not to distort the density estimation considerably. The sustained voltage-gated K+ conductance density was found to decrease steeply along the apical dendrite. The steep negative K+ conductance density gradient along the apical dendrite may help to define a distal, low-threshold region for amplification of distal synaptic input in L5B pyramidal neurones.

Animals↗
PubMed2006

Recording, analysis, and function of dendritic voltage-gated channels.

Ever since the publication of the Hamill et al. [Hamill et al., Pflügers Arch, 391:85-100, 1981] paper and the following increase in popularity of acute brain slice preparations, there has been a large increase in the volume of publications investigating voltage-gated channels in the central nervous system using the patch-clamp technique. In the preceding decade, investigations of voltage-gated channels have moved out of the somatic region into dendrites providing much needed information about dendritic voltage-gated channels. In this study, we review some aspects related to the investigation of voltage-gated ion channels in dendrites: recording, analysis, and function.

Action Potentials↗
PubMed2006

Pore properties and pharmacological features of the P2X receptor channel in airway ciliated cells.

Airway ciliated cells express an ATP-gated P2X receptor channel of unknown subunit composition (P2X(cilia)) which is modulated by Na+ and by long exposures to ATP. P2X(cilia) was investigated by recording currents from freshly dissociated rabbit airway ciliated cells with the patch-clamp technique in the whole-cell configuration. During the initial continuous exposure to extracellular ATP, P2X(cilia) currents gradually increase in magnitude (priming), yet the permeability to N-methyl-D-glucamine (NMDG) does not change, indicating that priming does not arise from a progressive change in pore diameter. Na+, which readily permeates P2X(cilia) receptor channels, was found to inhibit the channel extracellular to the electric field. The rank order of permeability to various monovalent cations is: Li+, Na+, K+, Rb+, Cs+, NMDG+ and TEA+, with a relative permeability of 1.35, 1.0, 0.99, 0.91, 0.79, 0.19 and 0.10, respectively. The rank order for the alkali cations follows an Eisenman series XI for a high-strength field site. Ca2+ has been estimated to be 7-fold more permeant than Na+. The rise in [Ca2+]i in ciliated cells, induced by the activation of P2X(cilia), is largely inhibited by either Brilliant Blue G or KN-62, indicating that P2X7 may be a part of P2X(cilia). P2X(cilia) is augmented by Zn2+ and by ivermectin, and P2X4 receptor protein is detected by immunolabelling at the basal half of the cilia, strongly suggesting that P2X4 is a component of P2X(cilia) receptor channels. Taken together, these results suggest that P2X(cilia) is either assembled from P2X4 and P2X7 subunits, or formed from modified P2X4 subunits.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2005

Constraining compartmental models using multiple voltage recordings and genetic algorithms.

Compartmental models with many nonlinearly and nonhomogeneous distributions of voltage-gated conductances are routinely used to investigate the physiology of complex neurons. However, the number of loosely constrained parameters makes manually constructing the desired model a daunting if not impossible task. Recently, progress has been made using automated parameter search methods, such as genetic algorithms (GAs). However, these methods have been applied to somatically recorded action potentials using relatively simple target functions. Using a genetic minimization algorithm and a reduced compartmental model based on a previously published model of layer 5 neocortical pyramidal neurons we compared the efficacy of five cost functions (based on the waveform of the membrane potential, the interspike interval, trajectory density, and their combinations) to constrain the model. When the model was constrained using somatic recordings only, a combined cost function was found to be the most effective. This combined cost function was then applied to investigate the contribution of dendritic and axonal recordings to the ability of the GA to constrain the model. The more recording locations from the dendrite and the axon that were added to the data set the better was the genetic minimization algorithm able to constrain the compartmental model. Based on these simulations we propose an experimental scheme that, in combination with a genetic minimization algorithm, may be used to constrain compartmental models of neurons.

Action Potentials↗
PubMed2005

Mutation of single murine acetylcholine receptor subunits reveals differential contribution of P121 to acetylcholine binding and channel opening.

The nicotinic acetylcholine receptor (AChR) is a heteropentameric, ligand-gated ion channel at the neuromuscular junction, where it is responsible for signal transduction between the motorneuron and the muscle. Point mutations in the subunits of the receptor change the channel's electrophysiological properties and underlie inherited forms of muscle weakness, the congenital myasthenic syndromes. One point mutation (P121L) has been identified in the epsilon-subunit of patients suffering from the fast-channel congenital myasthenic syndrome, which is evoked by reduced AChR openings. We introduced the P121L mutation into all murine AChR subunits and performed electrophysiological studies in Xenopus laevis oocytes. The P121L mutation in the epsilon-subunit of the adult mouse AChR affected ligand binding and channel gating in a manner similar to that described for human AChR. At equivalent positions in the alpha- and beta-subunits, the mutation caused only minor electrophysiological changes. Mutation of the delta-subunit had similar, but less pronounced functional consequences compared to epsilonP121L, reflecting the asymmetry of the acetylcholine binding sites and the dominant effect of the alpha-epsilon site on channel opening.

Acetylcholine↗
PubMed2004

Subthreshold inactivation of voltage-gated K+ channels modulates action potentials in neocortical bitufted interneurones from rats.

Voltage-gated K+ channels perform many functions in integration of synaptic input and action potential (AP) generation. In this study we show that in bitufted interneurones from layer 2/3 of the somatosensory cortex, the height and width of APs recorded at the soma are sensitive to changes in the resting membrane potential, suggesting subthreshold activity of voltage-gated conductances. Attributes of K+ currents examined in nucleated patches revealed a fast subthreshold-inactivating K+ conductance (K(f)) and a slow suprathreshold-inactivating K+ conductance (K(s)). Simulations of these K+ conductances, incorporated into a Hodgkin-Huxley-type model, suggested that during a single AP or during low frequency trains of APs, subthreshold inactivation of K(f) was the primary modulator of AP shape, whereas during trains of APs the shape was governed to a larger degree by K(s) resulting in the generation of smaller and broader APs. Utilizing the facilitating function of unitary pyramidal-to-bitufted cell synaptic transmission, single back-propagating APs were initiated in a bitufted interneurone by repeated stimulation of a presynaptic pyramidal cell. Ca2+ imaging and dendritic whole-cell recordings revealed that modulation of APs, which also affect the shape of back-propagating APs, resulted in a change in dendritic Ca2+ influx. Compartmental simulation of the back-propagating AP suggested a mechanism for the modulation of the back-propagating AP height and width by subthreshold activation of K(f). We speculate that this signal may modulate retrograde GABA release and consequently depression of synaptic efficacy of excitatory input from neighbouring pyramidal neurones.

Action Potentials↗
PubMed2003

Correction of conductance measurements in non-space-clamped structures: 1. Voltage-gated K+ channels.

To understand functions of a single neuron, such as propagation and generation of synaptic or action potentials, a detailed description of the kinetics and distribution of the underlying ionic conductances is essential. In voltage-clamp experiments, incomplete space clamp distorts the recorded currents, rendering accurate analysis impossible. Here, we present a simple numerical algorithm that corrects such distortions. The method performs a stepwise approximation of the conductance density at the site of a local voltage clamp. This is achieved by estimating membrane conductances in a simulation that yields simulated clamp currents, which are then fitted to the distorted recordings from the non-space-clamped structure, relying on accurately reconstructed cell morphology and experimentally determined passive properties. The method enabled accurate retrieval of the local densities, kinetics, and density gradients of somatic and dendritic channels. Neither the addition of noise nor variation of passive parameters significantly reduced the performance of the correction algorithm. The correction method was applied to two-electrode voltage-clamp recordings of K(+) currents from the apical dendrite of layer 5 neocortical pyramidal neurons. The generality and robustness of the algorithm make it a useful tool for voltage-clamp analysis of voltage-gated currents in structures of any morphology that is amenable to the voltage-clamp technique.

Algorithms↗