Search results for "Depolarization"
showing 3 items of 123 documents
Genetic analyses of the QT interval and its components in over 250K individuals identifies new loci and pathways affecting ventricular depolarization…
2021
AbstractThe QT interval is an electrocardiographic measure representing the sum of ventricular depolarization (QRS duration) and repolarization (JT interval). Abnormalities of the QT interval are associated with potentially fatal ventricular arrhythmia. We conducted genome-wide multi-ancestry analyses in >250,000 individuals and identified 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identified associations with Mendelian disease genes. Enrichments were observed in established pathways for QT and JT, with new genes indicated in insulin-receptor signalling and cardiac energy meta…
Cardiac pacemaker function of HCN4 channels in mice is confined to embryonic development and requires cyclic AMP.
2008
Important targets for cAMP signalling in the heart are hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels that underlie the depolarizing 'pacemaker' current, I(f). We studied the role of I(f) in mice, in which binding of cAMP to HCN4 channels was abolished by a single amino-acid exchange (R669Q). Homozygous HCN4(R669Q/R669Q) mice die during embryonic development. Prior to E12, homozygous and heterozygous embryos display reduced heart rates and show no or attenuated responses to catecholaminergic stimulation. Adult heterozygous mice display normal heart rates at rest and during exercise. However, following beta-adrenergic stimulation, hearts exhibit pauses and sino-atrial…
Endocannabinoid Role in Synaptic Plasticity and Learning
2009
Endocannabinoids have recently emerged as versatile modulators of synaptic transmission and can act as retrograde neurotransmitters. As they cannot be stored in synaptic vesicles, endocannabinoid signaling is believed to start ‘on-demand,’ via a stimulus-dependent synthesis from membranous precursors at the postsynaptic site. After synthesis, endocannabinoids bind presynaptically to cannabinoid type 1 (CB1) receptors, leading to a short- or long-term suppression of neurotransmitter release. CB1 receptors are present in a plethora of different synaptic connections in the brain. Electrophysiological and behavioral analyses of mutant mice lacking CB1 receptors and of pharmacologically treated …