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Spontaneous rhythmic activity in mammalian heart and brain depends on pacemaker currents (I(h)), which are produced by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. Here, we report that the mouse HCN2 pacemaker channel isoform also produced a large instantaneous current (I(inst(HCN2))) in addition to the well characterized, slowly(More)
Episodic Ataxia Type 1 is an autosomal dominant disorder characterized by episodes of ataxia and myokymia. It is associated with mutations in the KCNA1 voltage-gated potassium channel gene. In the present study, we describe a family with novel clinical features including persistent cerebellar dysfunction, cerebellar atrophy, and cognitive delay. All(More)
Hyperpolarization-activated cyclic nucleotide-gated (HCN) subunits produce a slowly activating current in response to hyperpolarization (If) and an instantaneous voltage-independent current (Iinst) when expressed in Chinese hamster ovary (CHO) cells. Here we found that a mutation in the S4-S5 linker of HCN2 (Y331D) produced an additional mixed cationic(More)
Despite permeability to both K(+) and Na(+), hyperpolarization-activated cyclic nucleotide-gated (HCN) pacemaker channels contain the K(+) channel signature sequence, GYG, within the selectivity filter of the pore. Here, we show that this region is involved in regulating gating in a mouse isoform of the pacemaker channel (mHCN2). A mutation in the GYG(More)
The aims of this study were: (a) to evaluate reliability of landmark location in digital processed images of film cephalograms of varying quality with that obtained in the films, and (b) to evaluate the pattern of error in landmark location with the two techniques. The sample consisted of 20 original cephalograms (OQ), 10 'high' quality images (Q1), and 10(More)
Pacemaker channels are formed by co-assembly of hyperpolarization-activated cyclic nucleotide-gated (HCN) subunits. Previously, we suggested that the NH(2) termini of the mouse HCN2 isoform were important for subunit co-assembly and functional channel expression. Using an alignment strategy together with yeast two-hybrid assays, patch clamp(More)
BACKGROUND A recent genome-wide association study identified a susceptibility locus for atrial fibrillation at the KCNN3 gene. Since the KCNN3 gene encodes for a small conductance calcium-activated potassium channel, we hypothesized that overexpression of the SK3 channel increases susceptibility to cardiac arrhythmias. METHODS AND RESULTS We characterized(More)
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels resemble Shaker K+ channels in structure and function. In both, changes in membrane voltage produce directionally similar movement of positively charged residues in the voltage sensor to alter the pore structure at the intracellular side and gate ion flow. However, HCNs open when(More)
Hyperpolarization-activated Cyclic Nucleotide-modulated (HCN) channels are similar in structure and function to voltage-gated potassium channels. Sequence similarity and functional analyses suggest that the HCN pore is potassium channel-like, consisting of a selectivity filter and an activation gate at the outer and inner ends, respectively. In(More)
Thermography of craniofacial region was taken in 33 patients with different types of craniofacial pain. In 26 patients (78%) a thermal asymmetry was found which corresponded to the painful area in 19 patients (57%). It can be concluded that temperature alterations in different areas of the face are common in such patients and are probably the consequence of(More)
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