SUBSTANCE-P PRODUCES AN INWARD CURRENT BY SUPPRESSING VOLTAGE-DEPENDENT AND VOLTAGE-INDEPENDENT K+ CURRENTS IN BULLFROG PRIMARY AFFERENT NEURONS

A whole-cell patch-clamp study was carried out to examine the effect o f substance P (SP) on the excitability of neurons in bullfrog dorsal r oot ganglia (DRG). SP (3 nM to 1 mu M) produced an inward current asso ciated with decreased membrane conductance at voltage range between -1 0 and -130 mV. Neurokinin A (NKA) and neurokinin B (NKB) also produced the inward current in DRG cells; the rank order of agonist potency wa s NKA=SP much greater than NKB. An antagonist for SP receptors, [D-Arg (1), D-Trp(7,9), Leu(11)]SP, did not prevent the response to SP. SP (3 nM to 1 mu M) suppressed the voltage-dependent non-inactivating K+ cu rrent, the M-current (I-M) by reducing the maximum M-conductance, A vo ltage-independent background K+ current, I-K(B), could be recorded at a hyperpolarizing voltage (less than or equal to-60 mV) from DRG neuro ns. SP (3 nM to 1 mu M) produced the inward current associated with de creased I-K(B) at a holding potential more negative than -60 mV. The S P-induced inward current reversed its polarity at the equilibrium pote ntial for K ions. Intracellular dialysis with Cs+ blocked the SP-induc ed responses. Depletion of intracellular ATP reduced SP-induced inward current. These results suggest that the SP-induced inward current was due to suppression of both the I-M and I-K(B) that are regulated by i ntracellular activity of ATP in bullfrog DRG neurons.