AJP - Cell Physiology, Vol 269, Issue 5 C1185-C1192, Copyright © 1995 by American Physiological Society
Suppression of a nonselective cation conductance by substance P in cochlear outer hair cells
S. Kakehata, T. Yamamoto, T. Takasaka and N. Akaike
Department of Neurophysiology, Tohoku University School of Medicine, Sendai, Japan.
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 3 x 10(-6) and 10(-4) M. SP decreased slope conductance
between -60 and +20 mV. Ion substitutions in the external medium revealed
that SP suppresses nonselective cation conductance with high permeability
for Ca2+. The relative ion permeability of the channel modulated by SP was
as follows: Ca2+ > Li+ approximately Cs+ approximately Na+ > Tris+.
The potency of the agonist action was as follows: SP >> neurokinin A
> neurokinin B. Peptide antagonists induced currents similar to those of
SP. CP-96345, a selective nonpeptide antagonist for the neurokinin type 1
receptor, did not inhibit the SP-induced current. Intracellular dialysis of
guanosine 5'-O-(2-thiodiphosphate) and pertussis toxin (PTX) suggests that
a PTX-insensitive G protein is involved in the SP response. Neither the
Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid nor
staurosporine (10(-6) M) affects 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 nonselective cation conductance in the lateral wall of OHCs
via a PTX-insensitive G protein.
