Nitric oxide inhibits na⁺ current of isolated baroreceptor neurons in culture

We have demonstrated previously that nitric oxide (NO) suppresses action potential discharge of baroreceptors (BR) in anesthetized rabbits. (Circ. Res. 76:42643, 1995). In the present study we investigated the ionic mechanism using whole cell patch-clamp technique on isolated BR neurons in culture. BR neurons were labeled in vivo by injecting fluorescent dye (Di-I) into aortic arch adventitia of rats two weeks before dissociation of the nodose ganglia. S-nitrosothiols were used as NO donors and delivered to cell bathing solution with a perfusion pump. At 100μM S-nitrosocysteine (cysNO), NO concentration in the bath solution measured by chemiluminescence was ∼2μM. Whole cell Na⁺ currents were measured during depolarization steps from a -60mV holding potential. D-cysNO (1-5×10^-4 M) inhibited peak Na⁺ current elicited at OmV to 59±7% of the control (n=8, p<0.01) in a reversible manner. The Na⁺ current was also inhibited by L-cysNO to a similar extent and by other NO donors (S-nitrosoglutathione and S-nitrosoacetylcysteine). Inhibition of the Na⁺ current was not associated with a change in the voltage-dependent activation. Neither cysteine nor cystine inhibited the Na⁺ current. The NO scavenger hemoglobin blunted the inhibitory effect of cysNO. These results indicate that NO inhibits Na⁺ current in BR neurons. This mechanism may mediate the NO-induced suppression of BR activity observed in vivo. These results also provide the first evidence that inhibition of Na⁺ current may represent a novel effector mechanism mediating responses to NO.