Suppression of a non selective cation conductance by substance p in
cochlear outer hair cells.
Kakehata, Seiji, Takehito Yamamoto, Tomonori Takasaka, and Norio
Akaike.
Department of Neurophysiology, and Department of
Otorhinolaryngology, Tohoku University School of Medicine, Sendai
980, Japan
APStracts 2:0195C, 1995.
Substance P (SP) hyperpolarizes outer hair cells (OHCs) of guinea-pig
cochlea. The cellular mechanisms of the SP response were investigated
with the whole-cell patch-clamp technique. SP induced outward
currents in a dose-dependent manner at a holding potential of -60 mV
in a concentration range between 3x10-6 M and 10-4 M. SP decreased a
slope conductance between -60 and +20 mV. Ion substitutions of the
external medium revealed that SP suppresses a non-selective cation
conductance with high permeability for Ca2+. The relative ion
permeability of the channel modulated by SP was in the order of;
Ca2+> Li+ nearly equal to Cs+ nearly equal to Na+> Tris+. The
potency of the agonist action was in the order of SP>>Neurokinin
A>Neurokinin B. Peptide antagonists induced currents similar to
those of SP. CP-96,345, a selective nonpeptide antagonist for the NK1
receptor, did not inhibit the ISP. Intracellular perfusion of
GDP[beta]S and pertussis toxin (PTX) suggest that a PTX-insensitive
G-protein is involved in the SP response. Neither the Ca2+ chelator
BAPTA nor staurosporine (10-6 M) affect the SP response. Local
application of SP by a puffer pipette indicates that the SP receptors
are distributed along the side of the OHC. These results suggest the
possibility that the action of SP on the OHCs may not be mediated by
the tachykinin receptors but rather by a tachykinin receptor
-independent pathway. It is proposed that SP suppresses the non
-selective cation conductance in the lateral wall of OHCs via a PTX
-insensitive G-proteins.
Received 16 December 1994; accepted in final form 24 April 1995.
APS Manuscript Number C722-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.