This study examined the responses of cultured adult human dorsal root
ganglion (hDRG) neurons to protons and capsaicin, two substances known
to produce pain and hyperalgesia in humans. Both substances were appl
ied to each neuron and responses were examined under both voltage- and
current-clamp recording conditions. Sensitivity to protons was tested
with rapid acidification of the extracellular fluid from pH 7.35 to 6
.0. In neurons nominally clamped near -60 mV, low pH evoked a transien
t inward current which, in all 40 hDRG neurons tested, was followed by
a more sustained inward current. The sustained current was associated
with an increase in membrane conductance in 10 neurons, a decrease in
27 neurons, and no overt change in conductance (< 10%) in 3 neurons.
Current-clamp recordings in the same neurons showed that the proton-in
duced sustained net inward current caused a prolonged depolarization o
f the membrane potential in all 40 hDRG neurons. The prolonged depolar
ization was associated with action potential discharge in 5 neurons. U
nlike low pH, capsaicin evoked a sustained net inward current in only
a subset of neurons tested (10 nM: 1/4, 30 nM: 4/8, 100 nM: 11/18, and
10 mu M: 10/10 neurons tested). The capsaicin-evoked currents were ac
companied by an increase in membrane conductance in 15 neurons, a decr
ease in 2, and no overt change in conductance in 9 neurons. Capsaicin
currents, like proton-induced currents, resulted in prolonged depolari
zations (10 nM: 0/4, 30 nM: 5/8, 100 nM: 8/18, and 10 mu M: 10/10 neur
ons tested). The depolarization resulted in the discharge of action po
tentials in 14 neurons. It is concluded that, while both protons and c
apsaicin exert excitatory effects on human sensory neurons, multiple m
embrane mechanisms lead to the depolarization of cultured hDRG neurons
by low pH. Inhibition of resting membrane conductances contributes to
the responses to low pH in some hDRG neurons.