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Fluid flow in the human body can be modeled using a water-level tank, a commonly used mechanistic approach in mechanical engineering for fluid transport processes. Postoperative fluid data from patients undergoing cardiac surgery is used to estimate fluid flow dynamics and total body water in the human body. This simplified model provide a basic understanding of the dynamics of fluid flow processes in the human body and could aid in modeling distribution of fluids in compartments.

This paper discusses possibilities to explain which Kv channels can be considered as first-order systems. This means that the dynamic behavior of these channels can be described with a first-order differential equation and are the most straightforward dynamical systems. For example, a typical first-order system is an RC circuit, and analogously, Kv channels can be considered with the dynamic behavior of first-order systems following RC circuits. This work represents a family of KV channels that can be described as first-order systems, providing an efficient method of ion channel modeling in computational electrophysiology.

Cancer cells typically exhibit altered ion channel expression and membrane potential, wich plays an important role in various processes such as proliferation or apoptosis Hence, therapeutic strategies that modulate ion channel activity or shift the membrane potential prove to be promising for cancer therapy. Since temperature significantly affects ion channel function, deviation from normal body temperture might provide akey factor in electrophysiological progression. In this pilot study, we focused on a first insight into the temperature-induced modulation of A549 cells using an automated patch clamp system. Measurements of 14 cells at hypo-, normo- and hypertermia were accomplished to investigate the temperature-dependent electophysiological behavior. The results revealed that both, temperatures below and above normal body temperature affect the current and potential of A549 cells. In hyperthermia the potential tends to more hyperpolarized values, while conversely, in hypothermic conditions we observer mainly a lower current reponse and thus a depolarization of the membrane potential.

In this paper, we present a control system theory based modeling approach for the voltage-gated ion-channel Kv10.1 at different temperatures. Kv10.1 is expressed in the central nervous system and the brain of healthy humans. The study of the activity of this ion channel is important, because its activity is associated with the occurrence of cancer in different organs or tissues. According to systems and control theory, the voltage-gated channel Kv10.1 was assumed to be a linear time-invariant system and, as such, exhibits dynamic behavior. The experimental results show that Kv10.1 operates as a first-order model based on the input voltage step protocol and the measured macroscopic ion current output.

Usability of medical devices is one of the main determining factors in preventing use errors in treatment and strongly correlates to patient safety and quality of treatment. This thesis demonstrates the usability testing and evaluation of a prototype for locomotor therapy of infants. Therefore, based on the normative requirements of the EN 62366, a concept combined of evaluation procedures and assessing methods was created to enable extensive testing and analysis of the different aspects of usability. On the basis of gathered information weak points were identified and appropriate measures were presented to increase the usability and operating safety of the locomotor prototype. The overall outcome showed an usability value of 77.4% and an evaluation score of 6.99, which can be interpreted as “satisfactory”.

A search in the GDC Data Portal revealed 304 documented somatic mutations of the KCNJ3 gene in primary tumors (out of 10.202 cases). Most affected tumor types were carcinomas from uterus, skin and lung, while breast cancer exerted the lowest number of somatic mutations. We focused our research on 15 missense mutations within the region between TM1 and TM2, comprising the pore helix and ion selectivity signature. Expression was measured by confocal laser scan microscopy of eGFP tagged GIRK1 subunits, expressed with and without GIRK4 in oocytes of Xenopus laevis. GIRK ion currents were activated via coexpressed m2Rs and measured by the Two Electrode Voltage Clamp technique. Magnitude of the total GIRK current, as well as the fraction of current inducible by the agonist, were measured. Ion selectivity was gauged by assessment of the PNa+/PK+ ratio, calculated by the GIRK current reversal potential in extracellular media at different Na+ and K+ concentrations. None of the tested mutations was able to form functional GIRK1 homooligomeric ion channels. One of the mutations, G145A, which locates directly to the ion selectivity signature, exerted an increased PNa+/PK+ ratio. Generally, the missense mutations studied can be categorized into three groups: (i) normal/ reduced expression accompanied by reduced/absent function (S132Y, F136L, E139K, G145A, R149Q, R149P, G178D, S185Y, Q186R), (ii) normal/increased expression as well as increased function (E140M, A142T, M184I) and (iii) miniscule expression but increased function relative to expression levels (I151N, G158S). We conclude, that gain of function mutations, identical or similar to categories (ii) and (iii), may potentially be involved in genesis and progression of malignancies in tissues that exert a high rate of occurrence of somatic mutations of KCNJ3. [ABSTRACT FROM AUTHOR]

Objective: This study aims to explore the potential of organic electrolytic photocapacitors (OEPCs), an innovative photovoltaic device, in mediating the activation of native voltage-gated Cav1.2 channels (I Ca,L ) in Guinea pig ventricular cardiomyocytes., Methods: Whole-cell patch-clamp recordings were employed to examine light-triggered OEPC mediated I Ca,L activation, integrating the channel's kinetic properties into a multicompartment cell model to take intracellular ion concentrations into account. A multidomain model was additionally incorporated to evaluate effects of OEPC-mediated stimulation. The final model combines external stimulation, multicompartmental cell simulation, and a patch-clamp amplifier equivalent circuit to assess the impact on achievable intracellular voltage changes., Results: Light pulses activated I Ca,L , with amplitudes similar to voltage-clamp activation and high sensitivity to the L-type Ca 2+ channel blocker, nifedipine. Light-triggered I Ca,L inactivation exhibited kinetic parameters comparable to voltage-induced inactivation., Conclusion: OEPC-mediated activation of I Ca,L demonstrates their potential for nongenetic optical modulation of cellular physiology potentially paving the way for the development of innovative therapies in cardiovascular health. The integrated model proves the light-mediated activation of I Ca,L and advances the understanding of the interplay between the patch-clamp amplifier and external stimulation devices., Significance: Treating cardiac conduction disorders by minimal-invasive means without genetic modifications could advance therapeutic approaches increasing patients' quality of life compared with conventional methods employing electronic devices.

A search in the GDC Data Portal revealed 304 documented somatic mutations of the KCNJ3 gene in primary tumors (out of 10.202 cases). Most affected tumor types were carcinomas from uterus, skin and lung, while breast cancer exerted the lowest number of somatic mutations. We focused our research on 15 missense mutations within the region between TM1 and TM2, comprising the pore helix and ion selectivity signature. Expression was measured by confocal laser scan microscopy of eGFP tagged GIRK1 subunits, expressed with and without GIRK4 in oocytes of Xenopus laevis . GIRK ion currents were activated via coexpressed m 2 Rs and measured by the Two Electrode Voltage Clamp technique. Magnitude of the total GIRK current, as well as the fraction of current inducible by the agonist, were measured. Ion selectivity was gauged by assessment of the P Na+ /P K+ ratio, calculated by the GIRK current reversal potential in extracellular media at different Na + and K + concentrations. None of the tested mutations was able to form functional GIRK1 homooligomeric ion channels. One of the mutations, G145A, which locates directly to the ion selectivity signature, exerted an increased P Na+ /P K+ ratio. Generally, the missense mutations studied can be categorized into three groups: (i) normal/reduced expression accompanied by reduced/absent function (S132Y, F136L, E139K, G145A, R149Q, R149P, G178D, S185Y, Q186R), (ii) normal/increased expression as well as increased function (E140M, A142T, M184I) and (iii) miniscule expression but increased function relative to expression levels (I151N, G158S). We conclude, that gain of function mutations, identical or similar to categories (ii) and (iii), may potentially be involved in genesis and progression of malignancies in tissues that exert a high rate of occurrence of somatic mutations of KCNJ3., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pelzmann, Hatab, Scheruebel, Langthaler, Rienmueller, Sokolowski, Gorischek, Platzer, Zorn-Pauly, Jahn, Bauernhofer and Schreibmayer.)