Cardiovascular sensitivity to general anesthetics is highly variable among individuals, but little is known about the genetics of anesthetic responses. Variable responses to anesthetics are also observed in animals. In this issue, Stadnicka et al., describe a study of the role of large conductance calcium and voltage-gated potassium (BK) channels in the cardiovascular response to the general anesthetic propofol. The article extends prior studies by the authors by showing that propofol hyperpolarizes vascular smooth muscle and that this response is accentuated in Dahl salt-sensitive (SS) rats compared with Brown Norway (BN) rats and appears to result from genes carried on a portion of chromosome 13. Propofol modulation of mesenteric arterial smooth muscle cells (MASMC) was evaluated, and the greater hyperpolarization of membrane potential in SS rats was blocked with a BK channel antagonist. The SS rats MASMC also exhibited greater calcium ion sensitivity and a larger whole-cell BK current density. In BN consomic strain rats, with the SS chromosome 13 substitution, the propofol sensitivity and BK channel properties converted to results similar to the background SS strain. The authors conclude that differential BK channel properties and expression underlie cardiovascular responses to propofol. The results support the suggestion that chromosome 13-associated genes are responsible for variable responses to propofol.
See article at J Pharmacol Exp Ther 2009, 330:727–735.
- The American Society for Pharmacology and Experimental Therapeutics