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T-type Ca channels are strongly expressed and important in the developing heart. In the adult heart, these channels play a significant role in pacemaker tissues, but there is uncertainty about their presence and physiological relevance in the working myocardium. Here, we show that the T-type Ca channel isoforms Cav3.1 and Cav3.2 are expressed at a protein level in ventricular cardiomyocytes from healthy adult C57/BL6 mice. Myocytes isolated from adult wild-type and Cav3.2 KO mice showed considerable whole cell T-type Ca currents under beta-adrenergic stimulation with isoprenaline. We further show that the detectability of basal T-type Ca currents in murine wild-type cardiomyocytes depends on the applied experimental conditions. Together, these findings reveal the presence of functional T-type Ca channels in the membrane of ventricular myocytes. In addition, electrically evoked Ca release from the sarcoplasmic reticulum was significantly impaired in Cav3.2 KO compared to wild-type cardiomyocytes. Our work implies a physiological role of T-type Ca channels in the healthy adult murine ventricular working myocardium.
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http://dx.doi.org/10.3390/membranes12060566 | DOI Listing |
Stem Cell Res
September 2025
The Florey, University of Melbourne, Melbourne, VIC, Australia; Praxis Precision Medicines, Cambridge, MA, USA. Electronic address:
The KCNT1 gene, affected in early-onset epilepsies, encodes a T-type sodium-activated potassium channel, K1.1, involved in membrane post-firing re-hyperpolarisation in various neuronal cell types. Fibroblasts from a boy with early-onset epilepsy carrying a heterozygous missense (R950Q) KCNT1 variant were reprogrammed using Sendai virus.
View Article and Find Full Text PDFBiomolecules
August 2025
Department of Anesthesiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
Although opioids are effective in treating pain, they cause serious side effects. The use of regional anesthesia, although effective in the perioperative period, may not be suitable if mobility and lack of numbness is desired. Hence, there is a clear need for novel pain therapies.
View Article and Find Full Text PDFSynlett
January 2025
Department of Organic Chemistry and Center for Molecular Biosciences, University of Innsbruck Innrain 80-82 6020 Innsbruck, Austria.
We present our synthetic endeavors towards the meroterpenoid ganoapplanin. This natural product was isolated from a fungus in 2016 and was found to be an inhibitor for T-type voltage-gated calcium channels. Our synthetic approach is based on a powerful intramolecular Giese cyclization/intermolecular aldol cascade to link the northern aromatic to the southern terpenoid fragment.
View Article and Find Full Text PDFSci Adv
August 2025
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by social deficits, repetitive behaviors, and comorbidities such as sensory abnormalities, sleep disturbances, and seizures. Although thalamocortical circuit dysfunction has been implicated in these symptoms, its precise roles in ASD pathophysiology remain poorly understood. Here, we examine the specific contribution of the reticular thalamic nucleus (RT), a key modulator of thalamocortical activity, to ASD-related behavioral deficits using a knockout mouse model.
View Article and Find Full Text PDFEpilepsia
August 2025
Simons Initiative for the Developing Brain, Patrick Wild Centre, Institute for Neuroscience and Cardiovascular Research, University of Edinburgh, Edinburgh, UK.
Objective: Pathogenic mutations in GRIN2B are an important cause of severe neurodevelopmental disorders resulting in epilepsy, autism, and intellectual disability. GRIN2B encodes the GluN2B subunit of N-methyl-d-aspartate receptors (NMDARs), which are ionotropic glutamate receptors critical for normal development of the nervous system and synaptic plasticity. Here, we characterized a novel Grin2b heterozygous knockout rat model with electroencephalography (EEG) and pharmacological interventions to block spontaneous seizures.
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