1,8-cineol effects on voltage-dependent potassium currents and action potential of mouse DRG neurons.

The 1,8-Cineole (CIN) is a terpenoid used in folk medicine due to its wide distribution in plants and that possess low toxicity. Its effect on voltage-dependet Na+ and Ca2+ channels and in the action potential (AP) of the neurons of rat superior cervical ganglion (SCG) have been reported, but the CIN effects on the potassium (K+) currents are not reported. Thus, this study had the objective to investigate the CIN effect on voltage dependent K+ current and on AP of mouse dorsal root ganglion (DRG) neurons. The project was submitted and approved by the CEUA/UECE (10312811/2022). Mus musculus mouse were used (male and female, mass: 30 to 40 g). For K+ current registry, the neurons of DRG were dissociated by the exposure to an enzymatic solution [type I collagenase (0.35 mg/ml) and trypisin (0.5 mg/ml)]. The neurons were plated on coverslips, incubated in a C02 enviroment at 37°C and used within 8 and 24 h. For the K+ current (IK+) electrophysiologic recordings, we used patch clamp technique in a whole cell mode, and the CIN (0.01 to 6.0 mM) was applied to cells by gravitational flow (0.3 to 0.8 mL/min). For the AP’s we used CIN at 3.0 mM. The CIN promoted partial blockade of IK+ in a concentration-dependent manner. The maximum blockade was 51.2 ± 5.7% at a concentration of 6.0 mM (n=6), reducing peak of IK+ and the sustained current from 7287 ± 2915.9 pA in control to 4614 ± 2283.1 pA and 6775 ± 2803.6 to 3916.6 ± 3916.6 pA, respectively. CIN 0.6 mM (n=6) had a percentual IK+ blockade of 19.5 ± 6.6 %, with the IK+ peak starting from 7381.7 ± 1832.6 pA to 5607.3 ± 1305.8 pA and a blockade of 30.5 ± 4.8% in the sustained current, from 6600.5 ± 1751.3 pA to 4338 ± 1113.4 pA. In CIN 0.1 mM (n=4) the IK+ showed an increase of 8.6 ± 7.1 % on IK+ peak, starting from 6794.2 ± 1494.7 pA to 7136.1 ± 1515.8 pA, but no significant blockade of sustained current. CIN 0.01mM (n=2) didn’t show a significant reduction on IK+ peak or sustained current. Regarding the AP, we had two effects: in some cells AP were blocked (n=3) and in the other they didn't (n=5). There was no change in resting membrane potential after exposure to CIN in these two groups of cells. The present study show that the CIN partially blocks the IK+ and the blockade of the current peak and sustained was similar. In addition, few cells had AP blockade in which it wasn’t followed by depolarization of the resting membrane potential, as seen on SCG. Due to GRD exhibits different cell types, with diferent expression of ion channels, it is likely that CIN acts on specific cell types, blocking excitability in these types of neuron.