CAPSAICIN-INDUCED MEMBRANE CURRENTS IN CULTURED SENSORY NEURONS OF THE RAT

Membrane currents induced by capsaicin (CAPS) in cultured sensory neur ons from 1- to 2-day-old rats were studied. Responses to CAPS (10 mu M ) exceeding 1 nA at -50 mV were found in smaller, usually bipolar or t ripolar neurons in which GABA (30 mu M) induced small or no response. Large, unipolar neurons, which exhibited large responses to GABA, were completely insensitive to CAPS (10 mu M). In contrast to GABA, respon ses to CAPS exhibited a slow rise and slow decay and a marked tachyphy laxis after repeated CAPS applications at high concentrations which ma de It difficult to study the concentration-response relationship. In p artially run-down neurons, which exhibited quasi stable responses, the slope of the ascending phase was concentration-dependent with an appa rent association rate constant K-1 9x10(4) [M(-1)s(-1)]. The time cons tant of the decay was 3.5 s, and was concentration-independent. Howeve r, in 5 neurones the EC(50) measured from the first series of CAPS app lications at increasing concentrations was 0.31+/-0.5 mu M with a Hill coefficient 1.66+/-0.35. The responses to CAPS reversed at +10.4+/-2. 5 mV suggesting that the current is carried nonselectively by monovale nt cations and Ca2+. The channel conductance of CAPS-gated channels at -50 mV calculated from the mean membrane current and variance of the current noise in outside-out patches or measured directly was 28 pS (n =5). It is suggested that the CAPS-gated channels are either controlle d by receptors with a very high affinity or that the channels are cont rolled by membrane-bound protein(s) which do not depend in their funct ion on the supply of GTP or other intracellular metabolites.