Details

Autor(en) / Beteiligte

• Ren, Ming
• Randolph, Aaron L
• Alvarez-Baron, Claudia
• Guo, Donglin
• Tran, Phu N
• Thiebaud, Nicolas
• Sheng, Jiansong
• Zhao, Jun
• Wu, Wendy W

Titel

Experimental factors that impact Ca.sub.V1.2 channel pharmacology-Effects of recording temperature, charge carrier, and quantification of drug effects on the step and ramp currents elicited by the "step-step-ramp" voltage protocol

Ist Teil von

• PloS one, 2022-11, Vol.17 (11), p.e0276995

Ort / Verlag

Public Library of Science

Erscheinungsjahr

2022

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• Ca.sub.V 1.2 channels contribute to action potential upstroke in pacemaker cells, plateau potential in working myocytes, and initiate excitation-contraction coupling. Understanding drug action on Ca.sub.V 1.2 channels may inform potential impact on cardiac function. However, literature shows large degrees of variability between Ca.sub.V 1.2 pharmacology generated by different laboratories, casting doubt regarding the utility of these data to predict or interpret clinical outcomes. This study examined experimental factors that may impact Ca.sub.V 1.2 pharmacology. All experimental factors examined affected Ca.sub.V 1.2 pharmacology. In addition, whole cell Ca.sub.V 1.2 current characteristics-rundown, temperature sensitivity, and impact of series resistance-are also factors that can impact pharmacology. Drug effects on Ca.sub.V 1.2 channels appear more complex than simple pore block mechanism. Normalizing laboratory-specific approaches is key to improve inter-laboratory data reproducibility. Releasing original electrophysiology records is essential to promote transparency and enable the independent evaluation of data quality.