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Updated: Jul 13, 2026
Analyses of Mitochondrial Calcium Influx in Isolated Mitochondria and Cultured Cells
Published on: April 27, 2018
The mitochondrial Ca2+-activated K+ channel activator, NS 1619 inhibits L-type Ca2+ channels in rat ventricular
Won Sun Park1, Sung Hyun Kang1, Youn Kyoung Son1
1National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondrial Research Group, Department of Physiology and Biophysics, College of Medicine, Biohealth Products Research Center, Cardiovascular and Metabolic Disease Center, Inje University, 633-165 Gaegeum-Dong, Busanjin-Gu, Busan 613-735, Republic of Korea.
Abstract:
We examined the effects of the mitochondrial Ca(2+)-activated K(+) (mitoBK(Ca)) channel activator NS 1619 on L-type Ca(2+) channels in rat ventricular myocytes. NS 1619 inhibited the Ca(2+) current in a dose-dependent manner. NS 1619 shifted the activation curve to more positive potentials, but did not have a significant effect on the inactivation curve. Pretreatment with inhibitors of membrane BK(Ca) channel, mitoBK(Ca) channel, protein kinase C, protein kinase A, and protein kinase G had little effect on the Ca(2+) current and did not alter the inhibitory effect of NS 1619 significantly. The application of additional NS 1619 in the presence of isoproterenol, a selective beta-adrenoreceptor agonist, reduced the Ca(2+) current to approximately the same level as a single application of NS 1619. In conclusion, our results suggest that NS 1619 inhibits the Ca(2+) current independent of the mitoBK(Ca) channel and protein kinases. Since NS 1619 is widely used to study mitoBK(Ca) channel function, it is essential to verify these unexpected effects of NS 1619 before experimental data can be interpreted accurately.
Insights
The mitochondrial BK(Ca) channel activator NS 1619 unexpectedly inhibits L-type Ca(2+) channels in rat heart cells, independent of known pathways. Verify these effects before interpreting NS 1619 data.
Area of Science:
- Cardiology
- Molecular Pharmacology
- Cell Physiology
Background:
- Mitochondrial Ca(2+)-activated K(+) (mitoBK(Ca)) channels are crucial in cellular energy regulation.
- NS 1619 is a commonly used activator to study mitoBK(Ca) channel function.
Purpose of the Study:
- To investigate the effects of NS 1619 on L-type Ca(2+) channels in rat ventricular myocytes.
- To determine if NS 1619's action on Ca(2+) channels is mediated by mitoBK(Ca) channels or protein kinases.
Main Methods:
- Electrophysiological recordings of Ca(2+) currents in rat ventricular myocytes.
- Dose-response analysis of NS 1619.
- Application of specific channel and kinase inhibitors.
- Co-application of NS 1619 with isoproterenol.
Main Results:
- NS 1619 inhibited L-type Ca(2+) current in a dose-dependent manner.
- NS 1619 shifted the activation curve of L-type Ca(2+) channels but not the inactivation curve.
- Inhibitors of membrane BK(Ca) channels, mitoBK(Ca) channels, and various protein kinases did not alter the inhibitory effect of NS 1619.
Conclusions:
- NS 1619 inhibits L-type Ca(2+) current independently of the mitoBK(Ca) channel and protein kinases.
- The findings highlight unexpected off-target effects of NS 1619.
- Accurate interpretation of experimental data using NS 1619 requires verification of these effects.
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