The mitochondrial Ca2+-activated K+ channel activator, NS 1619 inhibits L-type Ca2+ channels in rat ventricular myocytes.
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.
Park
Won Sun
WS
National 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.
Kang
Sung Hyun
SH
National 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.
Son
Youn Kyoung
YK
National 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.
Kim
Nari
N
National 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.
Ko
Jae-Hong
JH
National 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.
Kim
Hyoung Kyu
HK
National 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.
Ko
Eun A
EA
Department of Pharmacology, College of Medicine and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Busan, Republic of Korea.
Kim
Chi Dae
CD
Department of Pharmacology, College of Medicine and Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Busan, Republic of Korea.
Han
Jin
J
National 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. Electronic address: phyhanj@ijnc.inje.ac.kr.
D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000187:drug effects; D007545:Isoproterenol / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D001562:Benzimidazoles; D020746:Calcium Channels, L-Type; D015221:Potassium Channels; C086491:NS 1619; D017868:Cyclic AMP-Dependent Protein Kinases; D017869:Cyclic GMP-Dependent Protein Kinases; D011493:Protein Kinase C; D007545:Isoproterenol; D002118:Calcium