Activation of potassium conductance by ophiopogonin-D in acutely dissociated rat paratracheal neurones

Abstract

1. The effect of ophiopogonin-D (OP-D), a steroidal glycoside and an active component of Bakumondo-to, a Chinese herbal antitussive, on neurones acutely dissociated from paratracheal ganglia of 2-week-old Wistar rats was investigated using the nystatin-perforated patch recording configuration. 2. Under current-clamp conditions, OP-D (10 μM) hyperpolarized the paratracheal neurones from a resting membrane potential of -65.7 to -73.5 mV. 3. At the concentration of 1 μM and above, OP-D concentration-dependently activated an outward current accompanied by an increase in the membrane conductance under voltage-clamp conditions at a holding potential of -40 mV. 4. The reversal potential of the OP-D-induced current (IOP-D) was -79.4 mV, which is close to the K+ equilibrium potential of -86.4 mV. The changes in the reversal potential for a 10 fold change in extracellular K+ concentration was 53.1 mV, indicating that the current was carried by K+. 5. The IOP-D was blocked by an extracellular application of 1 mM Ba2+ by 59.0%, but other K+ channel blockers, including 4-aminopyridine (3 mM), apamin (1 μM), charybdotoxin (0.3 μM), glibenclamide (1 μM), tolbutamide (0.3 mM) and tetraethylammonium (10 mM), did not inhibit the IOP-D. 6. OP-D also inhibited the ACh- and bradykinin-induced depolarizing responses which were accompanied with firing of action potentials. 7. The results suggest that OP-D may be of benefit in reducing the excitability of airway parasympathetic ganglion neurones and consequently cholinergic control of airway function and further, that the hyperpolarizing effect of OP-D on paratracheal neurones via an activation of K+ channels might explain a part of mechanisms of the antitussive action of the agent.