Ionic basis of neurokinin-A-induced depolarization in single smooth muscle cells isolated from guinea-pig trachea.
Neurokinin A (NKA) caused single tracheal smooth muscle cells (TSMCs) to contract. The effects of NKA on the electrical activity of guinea-pig TSMCs were examined using the tight-seal whole-cell patch-clamp technique. Under current-clamp conditions at rest, the membrane potential of TSMCs spontaneously oscillated at about -40 mV and NKA rapidly depolarized the membrane potential to nearly 0 mV, which then gradually repolarized to about -20 mV in the presence of NKA. The oscillations in potential disappeared transiently during the rapid phase of depolarization in response to NKA and reappeared during the sustained phase of depolarization. Under voltage-clamp conditions, NKA evoked an inward current which faded quickly. Subsequently, the cell conductance in the presence of NKA at potentials greater than -40 mV decreased gradually. The reversal potential of the NKA-induced inward current was about 0 mV, and shifted with changes in the Cl- equilibrium potential. The Cl- current was not elicited by NKA when using a pipette solution containing 10 mM ethylenebis(oxonitrilo)tetraacetic acid (EGTA). During the sustained phase, K+ currents evoked by depolarizing voltage steps were inhibited by NKA. The present results indicate that NKA causes rapid and sustained depolarization of TSMCs by two distinct mechanisms: (1) initial transient activation of the Ca(2+)-dependent Cl- current, and (2) sustained inhibition of K+ currents.
D000818:Animals; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects*; D015288:Neurokinin A / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010456:Peptides, Cyclic / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D015320:Tachykinins / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000187:drug effects*
D018118:Chloride Channels; D010456:Peptides, Cyclic; D015221:Potassium Channels; D015320:Tachykinins; C075570:FK 224; D015288:Neurokinin A