Ketamine-induced cardiac depression is associated with increase in [Mg2+]i and activation of p38 MAP kinase and ERK 1/2 in guinea pig.
This study investigated the signaling pathways responsible for ketamine-induced cardiac depression in guinea pigs. The left ventricular development pressure (LVDP), velocity of the change in pressure (dP/dt), and heart rate (HR) accompanied with the total magnesium efflux ([Mg]e) were measured simultaneously in perfused hearts. The level of activation of the extracellular signal-regulated kinases 1/2 (ERK 1/2) and p38 mitogen-activated protein (MAP) kinase. The intracellular ionized magnesium concentration ([Mg2+]i) was measured using Mag-fura 2 AM in a single cardiomyocyte. Ketamine produced reversible decreases in the LVDP, dP/dt, and HR accompanied by increases in the [Mg]e. Ketamine also produced significant activation of p38 MAP kinase and ERK 1/2, and produced a dose-dependent increase in the [Mg2+]i, which was inhibited SB203580 and PD98059. These results suggest that ketamine-induced cardiac depression can be partly responsible for the increase in [Mg2+]i and [Mg]e, accompanied by the activation of p38 MAP kinase and ERK 1/2 in guinea pigs.
Kim
Shang-Jin
SJ
College of Veterinary Medicine, Chonbuk National University, Jeonju 561-756, Republic of Korea.
Kang
Hyung-Sub
HS
Lee
Mun-Young
MY
Lee
Sei-Jin
SJ
Seol
Jea-Won
JW
Park
Sang-Yeol
SY
Kim
In-Shik
IS
Kim
Nam-Soo
NS
Kim
Sung-Zoo
SZ
Kwak
Yong-Geun
YG
Kim
Jin-Shang
JS
D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007649:Ketamine / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D005419:Flavonoids; D007093:Imidazoles; D011725:Pyridines; D007649:Ketamine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D008274:Magnesium; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one