The intravenous anesthetic propofol inhibits human L-type calcium channels by enhancing voltage-dependent inactivation.
Propofol is commonly used to induce anesthesia but has been associated with some negative cardiovascular side effects, including negative inotropy, hypotension, and bradycardia. This study investigated the effect of propofol on L-type calcium current in acutely isolated human atrial myocytes to better understand the mechanism of these side effects. After informed consent was obtained, the atrial appendage was obtained from patients undergoing open-heart surgery who required cardiopulmonary bypass. Atrial myocytes were isolated using enzymatic digestion, and L-type calcium currents were recorded using the whole-cell patch clamp technique. Propofol enhanced the magnitude and speed of voltage-dependent inactivation of L-current. As a result, the propofol-induced inhibition was increased by protocols that increased inactivation such as longer voltage step duration, holding potential depolarization, and increased pulsing frequency. The preferential enhancement of L-channel inactivation by propofol can explain the associated cardiovascular side effects. The depolarized resting potential of arterial smooth muscle may render the L-channels in these cells particularly sensitive to propofol-induced inhibition, which could explain the hypotension observed in some patients. The enhancement of both inactivation kinetics and steady-state inactivation by propofol can also explain the negative inotropic effect. However, the enhanced voltage-dependent inactivation and use dependence could have beneficial effects for patients prone to certain arrhythmias and tachycardia.
Fassl
Jens
J
Department of Anesthesiology, Penn State Hershey Medical Center, Hershey, Pennsylvania, USA. jfassl@gmx.net
High
Kane M
KM
Stephenson
Edward R
ER
Yarotskyy
Viktor
V
Elmslie
Keith S
KS
D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000494:pharmacology*; D020517:Atrial Appendage / Q000187:drug effects* / Q000378:metabolism; D001919:Bradycardia / Q000139:chemically induced; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D004558:Electric Stimulation; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007700:Kinetics; D008564:Membrane Potentials; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D015742:Propofol / Q000009:adverse effects / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D015742:Propofol