Tachykinins activate nonselective cation currents in canine colonic myocytes.
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 33 degrees C, neurokinin A (NKA) and substance P (SP) reduced L-type Ca2+ current. NKA and SP activated a cationic current that reversed near 0 mV. This current (INKA or ISP, respectively) had properties similar to the acetylcholine (ACh)-activated nonselective 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+ (5 x 10(-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 nonselective cation conductance. These data suggest that a primary mechanism of the tachykinins is to activate a nonselective cation conductance that leads to depolarization. The increase in Ca2+ entry due to tachykinin stimulation appears to be secondary to the activation of the nonselective cation conductance.
Lee
H K
HK
Department of Physiology, University of Nevada School of Medicine, Reno 89557, USA.
Shuttleworth
C W
CW
Sanders
K M
KM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000502:physiology; D002412:Cations / Q000378:metabolism*; D003106:Colon / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004285:Dogs; D004553:Electric Conductivity; D005260:Female; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D015288:Neurokinin A / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D013373:Substance P / Q000494:pharmacology*
D015220:Calcium Channels; D002412:Cations; D013373:Substance P; D015288:Neurokinin A; D000109:Acetylcholine