M‐CURRENT IN NODOSE SENSORY NEURONS MEDIATES THE DEPOLARIZING EFFECT OF PROSTACYCLIN

Abstract

We have shown that carbacyclin (cPGI), a stable analog of prostacyclin, depolarizes baroreceptor nodose neurons and increases their excitability. The latter action is mediated by protein kinase A dependent inhibition of Maxi-K channels. In this study we asked whether the depolarizing effect of cPGI is mediated by inhibition of M-current. Linopirdine (30 μM), a selective direct inhibitor of M current, depolarized isolated nodose neurons by 17.6±5.8 mV (n=5, P<0.05) and decreased their conductance by 7.4±3.1 nS (P<0.05). cPGI (10 μM) did not depolarize the neurons in the presence of linopirdine suggesting that inhibition of M-current mediated the cPGI-induced depolarization. To verify this finding we used a patch clamp protocol for M-current detection. The neurons were voltage clamped at −20 mV and hyperpolarized with 500 msec pulses to −60 mV every 4 seconds. During the hyperpolarizing pulses, the current increased by 20.3±7.9 pA (n=8) over the period from 50 to 500 msec. In contrast, after linopirdine or after cPGI the current decreased by 20.2±7.8 (n=4) and 16.3±7.6 (n=4) pA, respectively. Application of cPGI in the presence of linopirdine did not alter the change in the current during the hyperpolarizing pulses. We conclude that linopirdine sensitive M-current is present in nodose sensory neurons and its inhibition mediates cPGI-induced depolarization (HL14388)