A Multifunctional Aromatic Residue in the External Pore Vestibule of Na+ Channels Contributes to the Local Anesthetic Receptor

2004 ◽  
Vol 67 (2) ◽  
pp. 424-434 ◽  
Author(s):  
S. Y. Tsang
Keyword(s):  
Local Anesthetic ◽  
Na Channels ◽  
Aromatic Residue

A Multifunctional Aromatic Residue in the External Pore Vestibule of Na+ Channels Contributes to the Local Anesthetic Receptor

2005 ◽  
Vol 67 (2) ◽  
pp. 424-434 ◽  
Author(s):  
Suk Ying Tsang ◽  
Robert G. Tsushima ◽  
Gordon F. Tomaselli ◽  
Ronald A. Li ◽  
Peter H. Backx
Keyword(s):  
Local Anesthetic ◽  
Na Channels ◽  
Aromatic Residue

Local Anesthetic Block of Batrachotoxin-Resistant Muscle Na+ Channels

1998 ◽  
Vol 54 (2) ◽  
pp. 389-396 ◽  
Author(s):  
Ging Kuo Wang ◽  
Catherine Quan ◽  
Sho-Ya Wang
Keyword(s):  
Local Anesthetic ◽  
Na Channels

Point Mutations at N434 in D1-S6 of μ1 Na+ Channels Modulate Binding Affinity and Stereoselectivity of Local Anesthetic Enantiomers

1999 ◽  
Vol 56 (2) ◽  
pp. 404-413 ◽  
Author(s):  
Carla Nau ◽  
Sho-Ya Wang ◽  
Gary R. Strichartz ◽  
Ging Kuo Wang
Keyword(s):  
Binding Affinity ◽  
Local Anesthetic ◽  
Point Mutations ◽  
Na Channels

Tonic Blocking Action of Meperidine on Na+and K+Channels in Amphibian Peripheral Nerves

2000 ◽  
Vol 92 (1) ◽  
pp. 147-147 ◽  
Author(s):  
Michael E. Bräu ◽  
E. Dietlind Koch ◽  
Werner Vogel ◽  
Gunter Hempelmann
Keyword(s):  
Peripheral Nerve ◽  
Local Anesthetic ◽  
Peripheral Nerves ◽  
Nerve Fibers ◽  
K Channel ◽  
Delayed Rectifier ◽  
Na Channel ◽  
Na Channels ◽  
K Channels ◽  
Local Anesthetic Agent

Background Among opioids, meperidine (pethidine) also shows local anesthetic activity when applied locally to peripheral nerve fibers and has been used for this effect in the clinical setting for regional anesthesia. This study investigated the blocking effects of meperidine on different ion channels in peripheral nerves. Methods Experiments were conducted using the outside-out configuration of the patch-clamp method applied to enzymatically prepared peripheral nerve fibers of Xenopus laevis. Half-maximal inhibiting concentrations were determined for Na+ channels and different K+ channels by nonlinear least-squares fitting of concentration-inhibition curves, assuming a one-to-one reaction. Results Externally applied meperidine reversibly blocked all investigated channels in a concentration-dependent manner, i.e., voltage-activated Na+ channel (half-maximal inhibiting concentration, 164 microM), delayed rectifier K+ channels (half-maximal inhibiting concentration, 194 microM), the calcium-activated K+ channel (half-maximal inhibiting concentration, 161 microM), and the voltage-independent flicker K+ channel (half-maximal inhibiting concentration, 139 microM). Maximal block in high concentrations of meperidine reached 83% for delayed rectifier K+ channels and 100% for all other channels. Meperidine blocks the Na+ channel in the same concentration range as the local anesthetic agent lidocaine (half-maximal inhibiting concentration, 172 microM) but did not compete for the same binding site as evaluated by competition experiments. Low concentrations of meperidine (1 nM to 1 microM) showed no effects on Na+ channels. The blockade of Na+ and delayed rectifier K+ channels could not be antagonized by the addition of naloxone. Conclusions It is concluded that meperidine has a nonselective inhibitory action on Na+ and K+ channels of amphibian peripheral nerve. For tonic Na+ channel block, neither an opioid receptor nor the the local anesthetic agent binding site is the target site for meperidine block.

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