We describe the construction of a dynamic clamp with a bandwidth of >125 kHz that utilizes a high-performance, yet low-cost, standard home/office PC interfaced with a high-speed (16 bit) data acquisition module. High bandwidth is achieved by exploiting recently available software advances (code-generation technology and optimized real-time kernel). Dynamic-clamp programs are constructed using Simulink, a visual programming language. Blocks for computation of membrane currents are written in the high-level MATLAB language; no programming in C is required. The instrument can be used in single- or dual-cell configurations, with the capability to modify programs while experiments are in progress. We describe an algorithm for computing the fast transient Na(+) current (I Na) in real time and test its accuracy and stability using rate constants appropriate for 37 °C. We then construct a program capable of supplying three currents to a cell preparation: I Na, the hyperpolarizing-activated inward pacemaker current (I f) and an inward-rectifier K(+) current (I K1). The program corrects for the IR drop due to electrode current flow and also records all voltages and currents. We tested this program on dual patch-clamped HEK293 cells where the dynamic clamp controls a current-clamp amplifier and a voltage-clamp amplifier controls membrane potential, and current-clamped HEK293 cells where the dynamic clamp produces spontaneous pacing behavior exhibiting Na(+) spikes in otherwise passive cells.
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http://dx.doi.org/10.1007/s00424-012-1186-8 | DOI Listing |
Sci Rep
January 2025
Department of Neurology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
Blood pressure (BP) is a dynamic measure that is frequently discussed in static terms. There exist many limitations in current documentation systems whereby documented BP values may not be reflective of the dynamic variability of BP. This study used an observational, prospective, non-randomized study design to examine the variability in BP response during intravenous vasoactive medication administration in an intensive care unit setting.
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January 2025
Department of Physiology and Neurobiology, Institute of Biology, Eötvös Loránd University, Pázmány Péter Sétány 1/C, Budapest, 1117, Hungary.
Neurons derived from induced pluripotent stem cells (h-iPSC-Ns) provide an invaluable model for studying the physiological aspects of human neuronal development under healthy and pathological conditions. However, multiple studies have demonstrated that h-iPSC-Ns exhibit a high degree of functional and epigenetic diversity. Due to the imprecise characterization and significant variation among the currently available maturation protocols, it is essential to establish a set of criteria to standardize models and accurately characterize and define the developmental properties of human neurons derived from iPSCs.
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January 2025
Infection and Global Health Division, School of Medicine, University of St Andrews, St Andrews, United Kingdom.
These case studies explore the subjective visual experiences of individuals with cerebral visual impairment (CVI), specifically dorsal stream dysfunction (DSD) characterized by simultanagnosia. Through three in-depth case studies, this work documents the challenges these individuals face when navigating cluttered environments. The individuals were asked to describe their visual experiences while watching videos of varying complexity, with the future aim of creating a simulation of simultanagnosia.
View Article and Find Full Text PDFJ Neurophysiol
January 2025
Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, Washington.
The persistent Na current (I) is thought to play important roles in many brain regions including the generation of inspiration in the ventral respiratory column (VRC) of mammals. The characterization of the slow inactivation of I requires long-lasting voltage steps (>1 s), which will increase intracellular Na and activate the Na/K-ATPase pump current (I). Thus, I may contribute to the previously measured slow inactivation of I and the generation of the inspiratory bursting rhythm.
View Article and Find Full Text PDFNat Chem Biol
January 2025
Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
Voltage-gated ion channels (VGICs) are crucial targets for neuropsychiatric therapeutics owing to their role in controlling neuronal excitability and the established link between their dysfunction and neurological diseases, highlighting the importance of identifying modulators with distinct mechanisms. Here we report two small-molecule modulators with the same chemical scaffold, Ebio2 and Ebio3, targeting a potassium channel KCNQ2, with opposite effects: Ebio2 acts as a potent activator, whereas Ebio3 serves as a potent and selective inhibitor. Guided by cryogenic electron microscopy, patch-clamp recordings and molecular dynamics simulations, we reveal that Ebio3 attaches to the outside of the inner gate, employing a unique non-blocking inhibitory mechanism that directly squeezes the S6 pore helix to inactivate the KCNQ2 channel.
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