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The location of a schizophrenia susceptibility locus at chromosome 22q11 has been suggested by genome-wide linkage studies. Additional support was provided by the observation of a higher-than-expected frequency of 22q11 microdeletions in patients with schizophrenia and the demonstration that approximately 20-30% of individuals with 22q11 microdeletions(More)
Neuropathic pain is a severe health problem for which there is a lack of effective therapy. A frequent underlying condition of neuropathic pain is a sustained overexcitability of pain-sensing (nociceptive) sensory fibres. Therefore, the identification of mechanisms for such abnormal neuronal excitability is of utmost importance for understanding neuropathic(More)
Kv3 potassium channels, with their ultra-rapid gating and high activation threshold, are essential for high-frequency firing in many CNS neurons. Significantly, the Kv3.4 subunit has been implicated in the major CNS disorders Parkinson's and Alzheimer's diseases, and it is claimed that selectively targeting this subunit will have therapeutic utility.(More)
Regulation of the resting membrane potential and the repolarization of neurons are important in regulating neuronal excitability. The potassium channel subunits Kv7.2 and Kv7.3 play a key role in stabilizing neuronal activity. Mutations in KCNQ2 and KCNQ3, the genes encoding Kv7.2 and Kv7.3, cause a neonatal form of epilepsy, and activators of these(More)
1. Miniature inhibitory postsynaptic currents (mIPSCs) were recorded in mouse Purkinje cells in the presence of 1 micro M tetrodotoxin (TTX). Under these conditions, which eliminated Ca(2+) influx through voltage-dependent Ca(2+) channels (VDCCs), the contribution of Ca(2+) stores to spontaneous GABA release was examined. 2. The plant alkaloid ryanodine(More)
Hyperpolarization-activated cyclic nucleotide gated (HCN) channel subunits are distributed widely, but selectively, in the central nervous system, and underlie hyperpolarization-activated currents (I(h)) that contribute to rhythmicity in a variety of neurons. This study investigates, using current and voltage-clamp techniques in brain slices from young(More)
Kv3 channels have a major role in determining neuronal excitability, and are characterized by ultra-rapid kinetics of gating and a high activation threshold. However, the gating currents, which occur as a result of positional changes of the charged elements in the channel structure during activation, are not well understood. Here we report a study of gating(More)
We describe how simple models of communication, consistent with known yeast physiological mechanisms, produce non-stationary, multimodal population densities, that are collected into an integer number of clusters. Theoretical analysis and numerical simulations demonstrate that the cell cycle progression of these clusters produces observable oscillation. We(More)
Robotic multiwell planar patch-clamp has become common in drug development and safety programs because it enables efficient and systematic testing of compounds against ion channels during voltage-clamp. It has not, however, been adopted significantly in other important areas of ion channel research, where conventional patch-clamp remains the favored method.(More)
Whole-cell patch clamp recordings were used to investigate the properties of a non-inactivating outward current observed in mouse cerebellar Purkinje neurones at a holding potential of -20 mV. Increasing the external potassium (K(+)) concentration from 3 mM to 20 mM produced a rightward shift in the observed reversal potential of approximately 30 mV or(More)