Increased Inhibition of Inward Rectifier K ⁺ Channels by Angiotensin II in Small-Diameter Coronary Artery of Isoproterenol-Induced Hypertrophied Model

Abstract

Objective-We investigated the effects of angiotensin II (Ang II) on inward rectifier K ϩ (Kir) channels in small-diameter coronary arterial smooth muscle cells (SCASMCs) of control and isoproterenol (Iso)-induced hypertrophied rabbits. Methods and Results-Kir current amplitude and Kir channel protein expression were definitely lower in the Iso-induced hypertrophied model than in the control. In a pressurized arterial experiment, 15 mmol/L K ϩ -induced vasodilation was greater in the control arteries than in the arteries of Iso-induced hypertrophied model. Ang II reduced the Kir current in a concentration-dependent manner, and this inhibition was greater in SCASMCs from Iso-induced hypertrophied model than from control. Although, there was no difference in the expression of Ang II type 2 (AT 2 ) receptor between SCASMCs of control and Iso-induced hypertrophied model, the expression of Ang II type 1 (AT 1 ) receptor and phosphorylated PKC␣ were greater in SCASMCs of Iso-induced hypertrophied model than of control. Conclusion-Ang II inhibits Kir channels more prominently in SCASMCs of Iso-induced hypertrophied model owing to increases in the expression of AT 1 receptor and the activation of PKC␣. Our findings about the differential expression of Kir channels and different modulation of Kir channels by a vasoconstrictor (Ang II) in a hypertrophy model are important for better understanding the responsiveness of small-diameter arteries during hypertrophy. (Arterioscler

Physiological roles of K⁺ channels in vascular smooth muscle cells

“…First, Kir channels contribute to the resting membrane potential and resting tone in small-diameter vascular smooth muscle. This hypothesis is supported by studies showing the constriction of small-diameter coronary and cerebral arteries at resting tone in response to Ba 2+ , a specific inhibitor of Kir channels (Park et al, 2007c, Park et al, 2007d.…”

“…In spite of the fact that BKCa channel function is believed to be enhanced by such pathological conditions as hypertension (Liu et al, 1998), some reports suggest that BKCa channel function is reportedly diminished in hypertrophy, (Kim et al, 2003) or is unaffected by ischemia (Bari et al, 1997). Recent evidence suggests that Kir channels are also affected by hypertension, ischemia, hypertrophy, and diabetes (McCarron and Halpern, 1990;Marrelli et al, 1998;Mayhan et al, 2004;Park et al, 2007c), but additional studies are necessary to establish a mechanism.…”

The Effects of the Selective Serotonin Reuptake Inhibitor Fluvoxamine on Voltage-Dependent K⁺ Channels in Rabbit Coronary Arterial Smooth Muscle Cells

“…Activation of Kir channels was also excludedbyusingcoronarysmoothmusclecellsisolatedfrom the second branch of the artery, known as the conduit artery, as the Kir channel has only been identified in small-diameter arteries. 17,18) Figure 1A shows representative Kv currents in coronary arterial smooth muscle cells. The Kv current rapidly reached a peak and showed slow and partial intrinsic inactivation.…”

A Carbohydrate Fraction, AIP1, fromArtemisia IwayomogiReduces the Action Potential Duration by Activation of Rapidly Activating Delayed Rectifier K+Channels in Rabbit Ventricular Myocytes

“…Single smooth muscle cells were isolated from rabbit coronary arteries as described previously [15]. Briefly, the coronary arteries were isolated from hearts and cleaned of connective tissue in the normal Tyrode solution under a stereomicroscope.…”