A 4-AP-sensitive current is enhanced by chronic carbon monoxide exposure in coronary artery myocytes.

A physiological role of carbon monoxide has been suggested for coronary myocytes; however, direct evidence is lacking. The objective of this study was to test the effect of chronic carbon monoxide exposure on the K(+) currents of the coronary myocytes. The effect of 3-wk chronic exposure to carbon monoxide was assessed on K(+) currents in isolated rat left coronary myocytes by the use of the patch-clamp technique in the whole cell configuration. Moreover, membrane potential studies were performed on coronary artery rings using intracellular microelectrodes, and coronary blood flow in isolated heart preparation was recorded. Carbon monoxide did not change the amplitude of global whole cell K(+) current, but it did increase the component sensitive to 1 mM 4-aminopyridine. Carbon monoxide exposure hyperpolarized coronary artery segments by approximately 10 mV and, therefore, increased their sensitivity to 4-aminopyridine. This effect was associated with an enhancement of coronary blood flow. We conclude that chronic carbon monoxide increases a 4-aminopyridine-sensitive current in isolated coronary myocytes. This mechanism could, in part, contribute to hyperpolarization and to increased coronary blood flow observed with carbon monoxide.

Mechanisms underlying the coronary vasodilation in the isolated perfused hearts of rats submitted to one week of high carbon monoxide exposure in vivo.

We examined the possible mechanisms for carbon monoxide (CO)-induced effects in hearts isolated from Wistar rats exposed for 1 wk to 530 ppm CO. They were treated by daily intraperitoneal injections of either methylene blue (10 mg/kg), glibenclamide (3 mg/kg), or apamin (125 nmol/kg), known to inhibit vasodilatory mechanisms. Hearts were excised, cannulated, and retrogradely perfused through the coronary artery, using the Langendorff method with a constant perfusion pressure. After stabilization, we investigated the degree of resistance to an in vitro transient global low-flow ischemia. One-week CO exposure induced a significant increase in hematocrit and a cardiomegaly, which were not affected by any of these drugs. An enhancement of coronary flow was observed concomitantly with a decrease in ischemic contracture after CO exposure. However, no improvement of contractile recovery was noted. Since methylene blue did not interact with the CO effects, a cGMP signaling pathway can be excluded. On the contrary, as glibenclamide and to a greater extend apamin blocked the vasodilatory effects of CO, we conclude that K+ channels may be involved in these CO effects.