Chronic carbon monoxide enhanced IbTx-sensitive currents in rat resistance pulmonary artery smooth muscle cells

Abstract

Exogenous carbon monoxide (CO) can induce pulmonary vasodilation by acting directly on pulmonary artery (PA) smooth muscle cells. We investigated the contribution of K+ channels to the regulation of resistance PA resting membrane potential on control (PAC) rats and rats exposed to CO for 3 wk at 530 parts/million, labeled as PACO rats. Whole cell patch-clamp experiments revealed that the resting membrane potential of PACO cells was more negative than that of PAC cells. This was associated with a decrease of membrane resistance in PACO cells. Additional analysis showed that outward current density in PACO cells was higher (50% at +60 mV) than in PAC cells. This was linked to an increase of iberiotoxin (IbTx)-sensitive current. Chronic CO hyperpolarized membrane of pressurized PA from -46.9 +/- 1.2 to -56.4 +/- 2.6 mV. Additionally, IbTx significantly depolarized membrane of smooth muscle cells from PACO arteries but not from PAC arteries. The present study provides initial evidence of an increase of Ca2+-activated K+ current in smooth muscle cells from PA of rats exposed to chronic CO.

Continuous inhalation of carbon monoxide attenuates hypoxic pulmonary hypertension development presumably through activation of BK channels

“…Recently, we have observed that chronic exogenous CO exposure could directly decrease the tone of coronary and PA [20,21]. Furthermore, we demonstrated that in small PA myocytes chronic exogenous CO also activates BK Ca currents [21]. Consistent with these observations, we demonstrated that chronic CO exposure of hypoxic rats increased the relaxation induced by acute CO of PA smooth muscle, a mechanism linked to an increase in K + -channels activity [22].…”

“…Zhang et al [19] demonstrated that an IbTx-sensitive current was decreased after inhibition of HO, suggesting that endogenous CO could activate vascular BK Ca currents. Recently, we have observed that chronic exogenous CO exposure could directly decrease the tone of coronary and PA [20,21]. Furthermore, we demonstrated that in small PA myocytes chronic exogenous CO also activates BK Ca currents [21].…”

“…Resistance PA with internal diameter less than 150 Am were isolated and prepared for membrane potential recording as previously described [21]. Endothelium was removed by air bubble passing inside the artery.…”

Carbon Monoxide: Endogenous Production, Physiological Functions, and Pharmacological Applications

“…In pulmonary artery SMC, the resting membrane potential is controlled by BK Ca channels and voltageactivated Kv channels (Bae et al, 1999). A 3-week exposure of pulmonary artery SMC to CO at 530 ppm hyperpolarized membrane potential and enhanced the iberiotoxin-sensitive whole-cell outward current without changing the membrane capacitance (Dubuis et al, 2002). The sensitivity of the whole-cell outward current to iberiotoxin, a selective blocker of BK Ca channels, suggested that CO induced expression and/or function (or both) of BK Ca channels in these cells.…”

Carbon Monoxide-Mediated Activation of Large-Conductance Calcium-Activated Potassium Channels Contributes to Mesenteric Vasodilatation in Cirrhotic Rats

“…Why the expression of ␣-subunit is increased in cirrhotic rats remains to be clarified. Dubuis et al (2002Dubuis et al ( , 2005 and Wu and Wang (2005) have hypothesized that the expression of BK Ca channels may be induced by high CO levels, a condition that might be present in the mesenteric circulation of cirrhotic rats. In conclusion, an overexpression of BK Ca ␣-subunits, together with HO-1 upregulation and increased CO production, participates in the endothelium-dependent alterations and mesenteric arterial vasodilatation of ascitic cirrhotic rats.…”