scholarly journals Drug Screening and Drug Safety Evaluation by Patch Clamp Technique

10.5772/35069 ◽  
2012 ◽  
Author(s):  
Yan Long ◽  
Zhiyuan Li
Keyword(s):  
Patch Clamp ◽  
Drug Safety ◽  
Drug Screening ◽  
Safety Evaluation ◽  
Patch Clamp Technique ◽  
Clamp Technique ◽  
Drug Safety Evaluation

Ketamine blocks Ca2+-activated K+ channels in rabbit cerebral arterial smooth muscle cells

2003 ◽  
Vol 285 (3) ◽  
pp. H1347-H1355 ◽  
Author(s):  
Jin Han ◽  
Nari Kim ◽  
Hyun Joo ◽  
Euiyong Kim
Keyword(s):  
Smooth Muscle ◽  
Patch Clamp ◽  
Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Muscle Cells ◽  
Channel Activity ◽  
Patch Clamp Technique ◽  
Arterial Smooth Muscle ◽  
Clamp Technique ◽  
Arterial Smooth Muscle Cells

Although ketamine and Ca2+-activated K+ (KCa) channels have been implicated in the contractile activity regulation of cerebral arteries, no studies have addressed the specific interactions between ketamine and the KCa channels in cerebral arteries. The purpose of this study was to examine the direct effects of ketamine on KCa channel activities using the patch-clamp technique in single-cell preparations of rabbit middle cerebral arterial smooth muscle. We tested the hypothesis that ketamine modulates the KCa channel activity of the cerebral arterial smooth muscle cells of the rabbit. Vascular myocytes were isolated from rabbit middle cerebral arteries using enzymatic dissociation. Single KCa channel activities of smooth muscle cells from rabbit cerebral arteries were recorded using the patch-clamp technique. In the inside-out patches, ketamine in the micromolar range inhibited channel activity with a half-maximal inhibition of the ketamine conentration value of 83.8 ± 12.9 μM. The Hill coefficient was 1.2 ± 0.3. The slope conductance of the current-voltage relationship was 320.1 ± 2.0 pS between 0 and +60 mV in the presence of ketamine and symmetrical 145 mM K+. Ketamine had little effect on either the voltage-dependency or open- and closed-time histograms of KCa channel. The present study clearly demonstrates that ketamine inhibits KCa channel activities in rabbit middle cerebral arterial smooth muscle cells. This inhibition of KCa channels may represent a mechanism for ketamine-induced cerebral vasoconstriction.

scholarly journals Benchmark dose-response analyses for multiple endpoints in drug safety evaluation

2021 ◽  
pp. 115732
Author(s):  
Antero Vieira Silva ◽  
Joakim Ringblom ◽  
Peter Moldeus ◽  
Elin Törnqvist ◽  
Mattias Öberg
Keyword(s):  
Drug Safety ◽  
Dose Response ◽  
Safety Evaluation ◽  
Benchmark Dose ◽  
Multiple Endpoints ◽  
Drug Safety Evaluation

Early Drug Safety Evaluation: Biomarkers, Signatures, and Fingerprints

2003 ◽  
Vol 35 (4) ◽  
pp. 269-275 ◽  
Author(s):  
Ruth Roberts ◽  
Kelvin Cain ◽  
Beth Coyle ◽  
Caroline Freathy ◽  
Jean-Francois Leonard ◽  
...  
Keyword(s):  
Drug Safety ◽  
Safety Evaluation ◽  
Drug Safety Evaluation ◽  
Early Drug
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