Annette C Dolphin

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The mouse mutant ducky, a model for absence epilepsy, is characterized by spike-wave seizures and ataxia. The ducky gene was mapped previously to distal mouse chromosome 9. High-resolution genetic and physical mapping has resulted in the identification of the Cacna2d2 gene encoding the alpha2delta2 voltage-dependent calcium channel subunit. Mutations in(More)
beta-Subunits of voltage-dependent Ca(2+) channels regulate both their expression and biophysical properties. We have injected a range of concentrations of beta3-cDNA into Xenopus oocytes, with a fixed concentration of alpha1B (Ca(V)2.2) cDNA, and have quantified the corresponding linear increase of beta3 protein. The concentration dependence of a number of(More)
Figure S1. Validation of anti-α1A immunostaining by shRNA-mediated knockdown of α1A. a, Confocal immunofluorescence images of a representative neuronal cell soma without (top) or with (bottom) transfection of vGpH+shRNAα1A and stained for anti-GFP (green; left) and anti-α1A (pseudo-colored; right) taken from the same dish. On average the(More)
1. The effect of intracellular application of the hydrolysis-resistant GTP and GDP analogues, guanosine 5'-O-3-thiotriphosphate (GTP-gamma-S), and guanosine 5'-O-2-thiodiphosphate (GDP-beta-S) has been examined on voltage-activated calcium-channel currents and the ability of the gamma-aminobutyric acid B agonist baclofen to inhibit them, in cultured rat(More)
Neuropathic pain is a debilitating condition affecting millions of people around the world and is defined as pain that follows a lesion or dysfunction of the nervous system. This type of pain is difficult to treat, but the novel compounds pregabalin (Lyrica) and gabapentin (Neurontin) have proven clinical efficacy. Unlike traditional analgesics such as(More)
Calcium influx into any cell requires fine tuning to guarantee the correct balance between activation of calcium-dependent processes, such as muscle contraction and neurotransmitter release, and calcium-induced cell damage. G protein-coupled receptors play a critical role in negative feedback to modulate the activity of the CaV2 subfamily of the(More)
Calcium channel β subunits have marked effects on the trafficking and on several of the biophysical properties of all high voltage activated calcium channels. In this article I shall review information on the different genes, on the structure of the β subunits, and on their differential expression and post-translational modification. Their role in(More)
Expression of the calcium channel Ca(V)2.2 is markedly suppressed by coexpression with truncated constructs of Ca(V)2.2. Furthermore, a two-domain construct of Ca(V)2.1 mimicking an episodic ataxia-2 mutation strongly inhibited Ca(V)2.1 currents. We have now determined the specificity of this effect, identified a potential mechanism, and have shown that(More)
We have examined the basis for G-protein modulation of the neuronal voltage-dependent calcium channels (VDCCs) alpha1E and alpha1B. A novel PCR product of alpha1E was isolated from rat brain. This contained an extended 5' DNA sequence and was subcloned onto the previously cloned isoform rbEII, giving rise to alpha1Elong whose N terminus was extended by 50(More)