Large-conductance Ca2+-activated K+ channel beta1-subunit knockout mice are not hypertensive.
Large-conductance Ca2+-activated K+ (BK) channels are composed of pore-forming α-subunits and accessory β1-subunits that modulate Ca2+ 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 β1-subunit knockout (BK β1-KO) mice were hypertensive. We evaluated 24-h mean arterial pressure (MAP) and heart rate in BK β1-KO mice using radiotelemetry. BK β1-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 β1-KO mice. In BK β1-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 β1-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 β1-KO mesenteric veins (MV). BK β1-subunits are not expressed in MV. The results indicate that BK β1-KO mice are not hypertensive on normal or high-salt intake. BK channel deficiency increases arterial reactivity to NE and L-type Ca2+ channel function in vitro, but the L-type Ca2+ channel modulation of MAP is not altered in BK β1-KO mice. BK and L-type Ca(2+) 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.
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA. xuhui2@msu.edu
Hui
H
Xu
Hannah
H
Garver
James J
JJ
Galligan
Gregory D
GD
Fink
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006321:Heart / Q000033:anatomy & histology; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D007763:Lac Operon / Q000235:genetics; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D008638:Mesenteric Arteries / Q000378:metabolism / Q000502:physiology; D008642:Mesenteric Veins / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D009126:Muscle Relaxation / Q000235:genetics / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D009929:Organ Size / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D014664:Vasodilation / Q000235:genetics / Q000502:physiology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; C543091:Kcnmb1 protein, mouse; D051038:Large-Conductance Calcium-Activated Potassium Channel beta Subunits; D026902:Potassium Channel Blockers; D009543:Nifedipine