December 1, 1995Circulation Research
Anti-minK Antisense Decreases the Amplitude of the Rapidly Activating Cardiac Delayed Rectifier K + Current
Why the study?
Does anti-minK antisense decrease the amplitude of the rapidly activating cardiac delayed rectifier K+ current in atrial tumor myocytes?
Population
Atrial tumor myocytes (AT-1 cells)
Comparison
Antisense oligonucleotides targeting the 5′… vs Corresponding sense oligonucleotide, random…
Design
Preclinical
Follow-up
24 to 48 hours
Authors
Discussion
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Implication
minK knockdown reduces IKr in atrial myocytes; leaves open its role in human arrhythmias or antiarrhythmic targeting.
Key Points
- To determine whether minK gene expression regulates cardiac delayed rectifier potassium currents in atrial tumor myocytes that naturally lack the slow delayed rectifier current.
- Exposed AT-1 atrial myocytes to antisense oligonucleotides targeting the translation start site of minK cDNA at concentrations from 50 to 10,000 nmol/L.
- Measured cell size, rapidly activating delayed rectifier potassium current (IKr), and L-type and T-type calcium currents 24 to 48 hours post-exposure against sense, random oligonucleotide, and untreated medium controls.
- At 1000 nmol/L, minK antisense significantly suppressed maximum IKr tail current amplitude to 2.5±0.1 pA/pF (mean±SEM, n=28) compared to 6.6±0.4 pA/pF in sense controls (n=27), 5.4±0.6 pA/pF in medium controls (n=21), and 5.8±0.7 pA/pF in random controls (n=9).
- Antisense exposure did not alter IKr activation, deactivation, rectification kinetics, or dofetilide sensitivity, and had no measurable effect on cell size or calcium currents.
Structured PICO
Does anti-minK antisense decrease the amplitude of the rapidly activating cardiac delayed rectifier K+ current in atrial tumor myocytes?
P
Population
Atrial tumor myocytes (AT-1 cells)
I
Intervention
Antisense oligonucleotides targeting the 5′ translation start site of the minK cDNA (50 to 10 000 nmol/L)
C
Comparator
Corresponding sense oligonucleotide, random oligonucleotide, or medium only
O
Outcome
Amplitude of rapidly activating delayed rectifier K+ current (IKr)surrogate
Antisense knockdown of minK in AT-1 cells significantly reduces IKr amplitude without affecting channel kinetics or calcium currents, indicating minK plays a role in determining IKr amplitude.
Cite This Study
Yang et al. (1995) studied this question.