Ionic basis of neurokinin-A-induced depolarization in single smooth muscle cells isolated from guinea-pig trachea.

Abstract

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.