Enhancement of gustatory nerve fibers to NaCl and formation of ion channels by commercial novobiocin.
Single fibers of the rat chorda tympani nerve were used to study the mechanism of action of the antibiotic novobiocin on salt taste transduction. In the rat, novobiocin selectively enhanced the responses of sodium-specific and amiloride-sensitive chorda tympani nerve fibers (N type) without affecting more broadly responsive cation-sensitive and amiloride-insensitive fibers (E type). In the presence of amiloride, novobiocin was ineffective at enhancing the response of N-type fibers toward sodium chloride. Novobiocin also increased the conductance of bilayers formed from neutral lipids by forming nonrectifying ion channels with low conductance (approximately 7 pS in 110 mM NaCl), long open times (several seconds and longer), and high cation selectivity. Amiloride did not alter either the conductance or kinetics of these novobiocin channels. These observations suggest that even though novobiocin is able to form cation channels in lipid bilayers, and possibly in cell membranes as well, its action on the salt-taste response is through modulation of existing amiloride-sensitive sodium channels.
Feigin
A M
AM
Monell Chemical Senses Center, University of Pennsylvania, Philadelphia.
Ninomiya
Y
Y
Bezrukov
S M
SM
Bryant
B P
BP
Moore
P A
PA
Komai
M
M
Wachowiak
M
M
Teeter
J H
JH
Vodyanoy
I
I
Brand
J G
JG
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002814:Chorda Tympani Nerve / Q000187:drug effects / Q000502:physiology*; D004553:Electric Conductivity / Q000187:drug effects; D066298:In Vitro Techniques; D015640:Ion Channel Gating; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008051:Lipid Bilayers; D008564:Membrane Potentials; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology*; D009675:Novobiocin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015222:Sodium Channels / Q000187:drug effects / Q000502:physiology; D012965:Sodium Chloride; D013649:Taste
D007473:Ion Channels; D008051:Lipid Bilayers; D015222:Sodium Channels; D009675:Novobiocin; D012965:Sodium Chloride; D000584:Amiloride