Tachykinins activate non-selective cation currents in canine
colonic myocytes.
Lee, Hye Kyung, C. William Shuttleworth, and Kenton M. Sanders.
Department of Physiology, University of Nevada School of Medicine,
Reno, Nevada 89557
APStracts 2:0247C, 1995.
The mechanism of tachykinin-induced excitation was studied in isolated
colonic muscle cells and intact muscle strips. In whole cell voltage
clamp studies performed at 33o C, NKA and SP reduced L -type Ca2&
current. NKA and SP activated a cationic current that reversed near 0
mV. This current (INKA or ISP) had properties similar to the non
-selective cation conductance (IACh) activated by muscarinic
stimulation in other gastrointestinal smooth muscle cells. INKA and
ISP were decreased when external Na& was reduced. In contrast to
IACh, INKA and ISP were not facilitated by increases in internal
Ca2&, but little or no current was activated by these peptides
when extracellular Ca2& was low. INKA (10-7 M) and ISP (10-5 M)
were blocked by Cd2& (5x10-4 M), quinine (10-3 M), and the
tachykinin receptor antagonist D-Pro2,D-TRP7,9-SP (10-5 M). Current
clamp recordings and intracellular recordings of intact tissues
showed that NKA and SP depolarized the cell membrane, which is
consistent with the activation of a non-selective cation conductance.
These data suggest that a primary mechanism of the tachykinins is to
activate a non-selective cation conductance which leads to
depolarization. The increase in Ca2& entry due to tachykinin
stimulation appears to be secondary to the activation of the non
-selective cation conductance.
Received 21 November 1994; accepted in final form 22 May 1995
APS Manuscript Number C0682-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 18 July 1995.