Electrophysiological effects of ketamine on human atrial myocytes at therapeutically relevant concentrations.
1. Ketamine is widely used for the induction of anaesthesia in high-risk patients with cardiovascular instability or severe hypovolaemia. However, the ionic mechanisms involved in the effects of ketamine at therapeutically relevant concentrations in human cardiac myocytes are unclear. The present study was designed to investigate the effects of ketamine on L-type Ca2+ (I(Ca)), transient outward K+ (I(to)), ultra-rapid delayed rectifier K+ (I(Kur)) and inward rectifier potassium (I(K1)) currents, as well as on action potentials, in human isolated atrial myocytes. 2. Atrial myocytes were isolated enzymatically from specimens of human atrial appendage obtained from patients undergoing coronary artery bypass grafting. The action potential and membrane currents were recorded in both current- and voltage-clamp modes using the patch-clamp technique. 3. Ketamine inhibited I(Ca) with an IC(50) of 1.8 micromol/L. In addition, 10 micromol/L ketamine decreased the I(Ca) peak current at +10 mV from 5.1 +/- 0.3 to 2.1 +/- 0.4 pA/pF (P < 0.01), but did not change the threshold potential, peak current potential and reverse potential. 4. Ketamine had no effect on I(to), I(Kur) or I(K1), but it reversibly shortened the duration of the action potential in human atrial myocytes. 5. In conclusion, ketamine, at a clinically relevant concentration, shortens the action potential duration of the human atrial myocytes, probably by inhibiting I(Ca).
Deng
Chun-Yu
CY
Research Center of Medical Sciences, Guangdong Provincial People's Hospital, Guangzhou, China.
Yu
Xi-Yong
XY
Kuang
Su-Juan
SJ
Rao
Fang
F
Yang
Min
M
Shan
Zhi-Xin
ZX
Qian
Wei-Min
WM
Zhou
Zhi-Ling
ZL
Lin
Qiu-Xiong
QX
Wu
Shu-Lin
SL
Zhang
You-Yi
YY
Lin
Shu-Guang
SG
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D022062:Electrophysiologic Techniques, Cardiac; D006325:Heart Atria / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use*; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors; D055815:Young Adult
D007649:Ketamine