Effect of nitric oxide on potassium channels of rat airway smooth muscle cells

Abstract

The effect of nitric oxide donor sodium nitroprusside (SNP) on resting membrane potential (Em) and potassium currents of the bronchial smooth muscle cells from rats was investigated. All experiments were conducted in conventional whole-cell configuration. The changes of Em and potassium currents after addition of 0.1 mmol/L SNP were measured under the current-clamp mode and the voltage-clamp mode respectively. Results showed that (1) SNP could decrease the Em from −33.8±7.4 mV to −43.7±6.7 mV (n=10,P<0.01); (2) SNP could increase the Ca²⁺-activated K⁺ channel peak currents under ramp protocol from 466.9±180. 1 pA to 597.7±237.6 pA (n=7,P<0.01), and the currents under pulse protocol at +50 mV were increased from 544.2±145.4 pA to 678.1±206.2 pA (n=6,P<0.05); (3) SNP also could increase voltage-gated K⁺ channel peak currents under ramp protocol from 389.6±84.1 pA to 526.7±98.7 pA (n=7,P<0.01), the currents under pulse protocol at +50 mV were increased from 275.7±85.2 pA to 444.3±128.5 pA (n=6,P<0.01). It was concluded that SNP increases the activities of Ca²⁺-activated K⁺ channels and voltage-gated K⁺ channels and leads to K⁺ efflux and hyperpolarization of the cell membrane, resulting in a decrease of the cell excitement.

Keywords

nitric oxide / airway smooth muscle / potassium channel

References

[1] SnetkovV A, HirstS J, WardJ P. Ion channels in freshly isolated and cultured human bronchial smooth muscle cells. Exp Physiol, 2002, 81(5): 791-791

[2] EllisJ L, ConananN D. Effect of potassium channel blockers on relaxations to a nitric oxide donor and to nonadrenergic nerve stimulation in guinea pig trachea. J Pharmacol Exp Ther, 1994, 271(2): 782-782

[3] ShikadaK, TanakaS. Potassium channel openers, NIP-121 and cromakalim, enhance the relaxation induced by sodium nitroprusside in the guinea pig isolated trachea. Br J Pharmacol, 1992, 107: 1116-1116

[4] YuanX J, TodM L, RobinL J, et al.. NO hyperpolarizes pulmonary artery smooth muscle cells and decreases the intracellular Ca²⁺ concentration by activating voltage-gated K⁺ channels. Proc Natl Acad Sci U S A, 2002, 93(19): 10489-10489

[5] PengW, HoidalJ R, FarruhkhI S. Regulation of Ca²⁺-activated K⁺ channels in pulmonary vascular smooth muscle cells: role of nitric oxide. J Appl Physiol, 2002, 81(3): 1264-1264

[6] BolotinaV M, NajibiS, PalacinoJ J, et al.. Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle. Nature, 1994, 368(6474): 850-850

[7] KrickS, PlatoshynO, SweeneyM, et al.. Nitric oxide induces apoptosis by activating K⁺ channels in pulmonary vascular smooth muscle cells. Am J Physiol, 2002, 282: H184-H184

[8] VanL E, MoyerM. Auxotonic contractile responses of rat tracheal and bronchial airway smooth muscle. Pulm Pharmacol Ther, 2001, 14(6): 443-443

[9] RishaniR, El-KhatibM, MrouehS. Treatment of severe status asthmaticus with nitric oxide. Pediatr Pulmonol, 1999, 28(6): 451-451