Nonselective cation channels coupled with tachykinin receptors in rat sensory neurons

1. Effects of substance P (SP) and other tachykinins on membrane currents were investigated using whole cell voltage clamp in cultured sensory neurons isolated from rat dorsal root ganglia. 2. SP (100 nM) evoked an inward current in two-thirds of the cells at negative potentials. In most of the cells that generated the inward current in response to SP, capsaicin also activated an inward current. The SP-evoked inward current was not observed in cells loaded with 2 mM guanosine 5'-O-(2-thiodiphosphate) (GDP beta S). 3. Neurokinin A (NKA) or neurokinin B (NKB) also activated an inward current. At 100 nM of each agonist, the order was NKB > NKA > SP with respect to activated current amplitude. 4. The tachykinin-activated current was reversed around +10 mV with a standard extracellular solution containing 140 mM NaCl. The reversal potential became more negative when extracellular NaCl was reduced by substituting with sucrose. The inward current was also activated in cells bathed in an extracellular solution containing Cs+, tetraethylammonium (TEA) or N-methyl-D-glucamine (NMDG) as a major cation instead of Na+. The order of permeability, determined from the reversal potential of the current, was Cs+ not equal to Na+ > TEA > NMDG. The amplitude of the inward current activated by NKB was increased when extracellular Na+ was replaced with Cs+, TEA or NMDG. 5. Permeability of Ca2+ was tested using an extracellular solution containing Ca2+ as the only cation (111.8 mM Ca2+ outside). Under this condition, NKB evoked an inward current that reversed around +30 mV. 6. The results suggest that SP and other tachykinins activate nonselective cation channels, which are also permeable to Ca2+, through receptors which are more responsive to NKB than to SP or NKA. The channel activation may serve as a mechanism underlying tachykinin-mediated excitatory neurotransmission in sensory neurons.