The interaction of local anesthetics with the ryanodine receptor of the sarcoplasmic reticulum |
| |
Authors: | Varda Shoshan-Barmatz Sigalit Zchut |
| |
Institution: | (1) Department of Life Sciences, Ben Gurion University of the Negev, 84 105 Beer Sheva, Israel |
| |
Abstract: | The effects of various local anesthetics (LAs) on the skeletal muscle ryanodine receptor were tested. The LAs were divided into three categories according to their effects on the binding of ryanodine to the junctional sarcoplasmic reticulum membranes. Ryanodine binding was assayed in the presence of 0.2 m NaCl and 10 m CaCl2. Tetracaine and dibucaine inhibit the binding with half-maximal inhibition (CI50) of 0.12 and 0.25 mm, respectively, while inhibition by benzocaine and procaine occurs with CI50 of about 10-fold higher. Lidocaine, its analogue QX-314, and prilocaine, on the other hand, stimulate the binding up to fourfold with half-maximal stimulation occurring with about 2 mm of the drugs. Lidocaine increases both the receptor affinity for ryanodine by about fivefold and the rate of ryanodine association with its binding site by about 10-fold.Tetracaine interacts with the ryanodine receptor in a non-competitive fashion with respect to ryanodine but it competes with lidocaine for its binding site, suggesting the existence of a single site for the inhibitory and stimulatory LA. |
| |
Keywords: | local anesthetics ryanodine receptor sarcoplasmic reticulum Ca2+ release channel |
本文献已被 SpringerLink 等数据库收录! |
|