Large - conductance Ca 2 - activated K channel 1 - subunit knockout mice are not hypertensive

Xu H, Garver H, Galligan JJ, Fink GD. Large-conductance Ca activated K channel 1-subunit knockout mice are not hypertensive. Am J Physiol Heart Circ Physiol 300: H476–H485, 2011. First published December 3, 2010; doi:10.1152/ajpheart.00975.2010.—Large-conductance Ca -activated K (BK) channels are composed of poreforming -subunits and accessory 1-subunits that modulate Ca sensitivity. BK channels regulate arterial myogenic tone and renal Na clearance/K reabsorption. Previous studies using indirect or short-term blood pressure measurements found that BK channel 1-subunit knockout (BK 1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK 1-KO mice using radiotelemetry. BK 1-KO mice did not have a higher 24-h average MAP when compared with wild-type (WT) mice, although MAP was 10 mmHg higher at night. The dose-dependent peak declines in MAP by nifedipine were only slightly larger in BK 1-KO mice. In BK 1-KO mice, giving 1% NaCl to mice to drink for 7 days caused a transient (5 days) elevation of MAP ( 5 mmHg); MAP returned to pre-saline levels by day 6. BK 1-KO mesenteric arteries in vitro demonstrated diminished contractile responses to paxilline, increased reactivity to Bay K 8644 and norepinephrine (NE), and maintained relaxation to isoproterenol. Paxilline and Bay K 8644 did not constrict WT or BK 1-KO mesenteric veins (MV). BK 1subunits are not expressed in MV. The results indicate that BK 1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca channel function in vitro, but the L-type Ca channel modulation of MAP is not altered in BK 1-KO mice. BK and L-type Ca channels do not modulate murine venous tone. It appears that selective loss of BK channel function in arteries only is not sufficient to cause sustained hypertension.