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

Abstract

1 The e ect 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 con®guration. 2 Under current-clamp conditions, OP-D (10 mM) hyperpolarized the paratracheal neurones from a resting membrane potential of 765.7 to 773.5 mV.3 At the concentration of 1 mM 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 740 mV. 4 The reversal potential of the OP-D-induced current (I OP-D ) was 779.4 mV, which is close to the K + equilibrium potential of 786.4 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 I OP-D was blocked by an extracellular application of 1 mM Ba 2+ by 59.0%, but other K + channel blockers, including 4-aminopyridine (3 mM), apamin (1 mM), charybdotoxin (0.3 mM), glibenclamide (1 mM), tolbutamide (0.3 mM) and tetraethylammonium (10 mM), did not inhibit the I OP-D . 6 OP-D also inhibited the ACh-and bradykinin-induced depolarizing responses which were accompanied with ®ring of action potentials. 7 The results suggest that OP-D may be of bene®t in reducing the excitability of airway parasympathetic ganglion neurones and consequently cholinergic control of airway function and further, that the hyperpolarizing e ect 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.

An electrophysiological study of muscarinic and nicotinic receptors of rat paratracheal ganglion neurons and their inhibition by Z‐338

“…The procedure for obtaining dissociated paratracheal ganglion neurons is similar to that described elsewhere (Aibara et al ., 1992; Ishibashi et al ., 2001). Briefly, the paratracheal ganglia were rapidly removed from the trachea of 2‐week‐old Wistar rats under ether anaesthesia, and the rats were subsequently killed by exsanguination.…”

“…Patch pipettes were prepared using a vertical micropipette puller (PB‐7, Narishige, Tokyo, Japan). The resistance between the patch pipette filled with the internal solution and the reference electrode in the normal external solution was 2 – 4 MΩ and was compensated in same manner explained by Ishibashi et al . (2001).…”

Central and peripheral mechanisms of narcotic antitussives: codeine-sensitive and -resistant coughs

“…Thus, the PTG are thought to be not only a relay neuron of the parasympathetic nerve, but also integrative sites for the neuromodulation of normal airway function and important for pathogenesis in airway inflammation. Interestingly, ophiopogonin-D, an active constituent of bakumondo-to, a Chinese herbal medicine, hyperpolarized the membrane potential via activation of the K + current, reducing the cell excitability of PTG neurons [52]. Bakumondo-to is found to be effective for treating clinically chronic coughs [53,54], and to inhibit codeine-registrant coughs as that expressed in the experimental model described above [55,56].…”

Scillapersicene: a new homoisoflavonoid with cytotoxic activity from the bulbs ofScilla persicaHAUSSKN

“…These compounds were mainly discovered from plants belonging to the Liliaceae family and a few other plant species (Sievänen et al 2010). Homoisoflavonoids have been reported to display multiple biological properties such as antioxidant activity (Siddaiah et al 2006;Zhou et al 2008), cytotoxic activity (Nguyen et al 2006;Yan et al 2012;Hafez Ghoran et al 2014), inhibition of platelet aggregation (Kou et al 2006), cough sedative (Ishibashi et al 2001), hyperglycemia (Choi et al 2004), anti-angiogenic (Shim et al 2004), anti-fungal (Srinivas et al 2003), anti-inflammatory, antiallergic, antihistaminic, angioprotective activities, and have been detected as potent phosphodiesterase inhibitors (Della Loggia et al 1989;Amschler et al 1996;Shim et al 2004). Many natural products have traditionally played a prominent role in drug discovery and were the basis of most early medicines (Grabley & Thiericke 1999;Buss et al 2003).…”