Increasing evidence suggests that cardiac pacemaking is the result of two sinoatrial node (SAN) cell mechanisms: a 'voltage clock' and a Ca(2+) dependent process, or 'Ca(2+) clock.' The voltage clock initiates action potentials (APs) by SAN cell membrane potential depolarization from inward currents, of which the pacemaker current (I(f)) is thought to be particularly important. A Ca(2+) dependent process triggers APs when sarcoplasmic reticulum (SR) Ca(2+) release activates inward current carried by the forward mode of the electrogenic Na(+)/Ca(2+) exchanger (NCX). However, these mechanisms have mostly been defined in rodents or rabbits, but are unexplored in single SAN cells from larger animals. Here, we used patch-clamp and confocal microscope techniques to explore the roles of the voltage and Ca(2+) clock mechanisms in canine SAN pacemaker cells. We found that ZD7288, a selective I(f) antagonist, significantly reduced basal automaticity and induced irregular, arrhythmia-like activity in canine SAN cells. In addition, ZD7288 impaired but did not eliminate the SAN cell rate acceleration by isoproterenol. In contrast, ryanodine significantly reduced the SAN cell acceleration by isoproterenol, while ryanodine reduction of basal automaticity was modest ( approximately 14%) and did not reach statistical significance. Importantly, pretreatment with ryanodine eliminated SR Ca(2+) release, but did not affect basal or isoproterenol-enhanced I(f). Taken together, these results indicate that voltage and Ca(2+) dependent automaticity mechanisms coexist in canine SAN cells, and suggest that I(f) and SR Ca(2+) release cooperate to determine baseline and catecholamine-dependent automaticity in isolated dog SAN cells.
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http://dx.doi.org/10.1016/j.yjmcc.2010.03.019 | DOI Listing |
J Mol Cell Biol
January 2025
Department of Endocrinology, Beijing Diabetes Institute, Beijing Key Laboratory of Diabetes Research and Care, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Insulin secretion is mainly regulated by two electrophysiological events, depolarization initiated by the closure of ATP-sensitive K+ (KATP) channels and repolarization mediated by K+ efflux. Quinine, a natural component commonly used for the treatment of malaria, has been reported to directly stimulate insulin release and lead to hypoglycemia in patients during treatment through inhibiting KATP channels. In this study, we verified the insulinotropic effect of quinine on the isolated mouse pancreatic islets.
View Article and Find Full Text PDFExp Eye Res
January 2025
Department of Basic and Translational Science, Philadelphia, PA, 19104, United States; Department of Physiology, Philadelphia, PA, 19104, United States. Electronic address:
The P2X7 receptor (P2X7R) for extracellular ATP is implicated in several forms of retinal degeneration, including diabetic retinopathy, age-related macular degeneration, and glaucoma. P2X7R stimulation can trigger release of master cytokine IL-1β from microglia in the brain and from macrophages, but evidence of release from retinal microglia is indirect. Isolated mouse and rat retinal microglia, and wholemounts from CX3CR1 mice, were examined to determine if ATP induced IL-1β release directly from retinal microglial cells and if it also primed expression of IL-1β on an mRNA and protein level.
View Article and Find Full Text PDFJ Hazard Mater
January 2025
Department of Civil and Environmental Engineering, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea; Department of Environmental Engineering, Graduate School, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 05029, Republic of Korea. Electronic address:
The synthesis of coal bottom ash-induced zeolite (Si-Al material) has been widely reported; however, the selective recovery of the three main elements, viz., Si, Al, and Fe, from coal bottom ash for the synthesis of reactive adsorbents has not yet been reported. In this study, we separated the magnetic and non-magnetic fractions of coal bottom ash to selectively recover Fe and Si-Al for synthesizing nanoscale zero-valent iron@zeolite (NZVI@ZBA) composites with uniform formation of Fe(0) nanoparticles on the ZBA surface.
View Article and Find Full Text PDFCarbohydr Polym
March 2025
Department of Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan; Department of Ophthalmology, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan; Department of Materials Engineering, Ming Chi University of Technology, New Taipei City 24301, Taiwan; Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 33303, Taiwan; Center for Biomedical Engineering, Chang Gung University, Taoyuan 33302, Taiwan. Electronic address:
In this study, we aimed to develop ion-responsive and biocompatible alginate-capped nanoceria (Ce-ALG) for β-1,3-glucan (i.e., wound healing agent) delivery and corneal abrasion (CA) treatment.
View Article and Find Full Text PDFInt J Biol Macromol
January 2025
Key Laboratory of Fermentation Engineering (Ministry of Education), Cooperative Innovation Center of Industrial Fermentation (Ministry of Education & Hubei Province), National "111" Center for Cellular Regulation and Molecular Pharmaceutics, Glyn O. Phillips Hydrocolloid Research Centre at HBUT, School of Life and Health Sciences, Hubei University of Technology, Wuhan, 430068, China; Ministry-of-Education Key Laboratory for the Green Preparation and Application of Functional Materials, Hubei Key Laboratory of Polymer Materials, College of Health Science and Engineering, School of Materials Science and Engineering, Hubei University, Wuhan 430062, China. Electronic address:
Calcium-based nanomaterials-mediated Ca overload-induced pyroptosis and its application in tumor therapy have received considerable attention. However, the calcium buffering capacity of tumor cells can maintain mitochondrial calcium homeostasis, so it is important to effectively disrupt this homeostasis to activate pyroptosis. Here, a nano-modulator CUR@CaCO-PArg@HA (CCAH) was developed to regulate calcium overload in multiple channels and activate pyroptosis.
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