SKCa and IKCa Channels, myogenic tone, and vasodilator responses in middle cerebral arteries and parenchymal arterioles: effect of ischemia and reperfusion.
OBJECTIVE
The role of SK(Ca) and IK(Ca) channels in myogenic tone and endothelium-derived hyperpolarizing factor (EDHF) responsiveness was investigated under control conditions and after ischemia and reperfusion in parenchymal arterioles (PA) versus middle cerebral arteries (MCA).


METHODS
MCA and PA were dissected from male Wistar rats that were ischemic for 1 hour with 24 hours of reperfusion (n=12) or sham controls (n=12). Basal tone and reactivity to apamin (300 nmol/L), TRAM-34 (1.0 micromol/L), and nitro-L-arginine (0.1 mmol/L) were compared in PA and MCA pressurized to 40 mm Hg and 75 mm Hg, respectively. SK(Ca) and IK(Ca) channel mRNA expression was measured using real-time PCR.


RESULTS
PA developed greater basal tone than MCA (42+/-4% versus 19+/-3%; P<0.01). Addition of apamin and TRAM-34 increased tone of PA by 25+/-3% and 16+/-2%, respectively, whereas MCA had no response to either inhibitor. After ischemia and reperfusion, the response to nitric oxide synthase inhibition (NOS) was diminished in PA, whereas EDHF responsiveness was preserved. In addition, stimulated EDHF dilation was partially reversed by apamin and completely reversed by TRAM-34 in both control and ischemic PA. SK(Ca) and IK(Ca) channel mRNA expression was similar in PA and MCA and not altered by ischemia and reperfusion. However, IK(Ca) channel mRNA expression was 4- to 5-fold greater than SK(Ca) channels.


CONCLUSIONS
It appears that SK(Ca) and IK(Ca) channel activity diminishes basal tone of PA, but not MCA. The preservation of EDHF responsiveness of PA after ischemia and reperfusion suggests an important role for this vasodilator under conditions when NOS is inhibited.
Cipolla
Marilyn J
MJ
Department of Neurology, University of Vermont, Burlington, VT 05405, USA. Marilyn.Cipolla@uvm.edu
Smith
Jeremiah
J
Kohlmeyer
Meghan M
MM
Godfrey
Julie A
JA
D000818:Animals; D001030:Apamin / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D001685:Biological Factors / Q000378:metabolism; D002545:Brain Ischemia / Q000503:physiopathology*; D000001:Calcimycin / Q000494:pharmacology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D020768:Middle Cerebral Artery / Q000502:physiology; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000503:physiopathology*; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000235:genetics / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D001685:Biological Factors; D004791:Enzyme Inhibitors; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D007476:Ionophores; D011720:Pyrazoles; D012333:RNA, Messenger; D051640:Small-Conductance Calcium-Activated Potassium Channels; C411671:TRAM 34; C067410:endothelium-dependent hyperpolarization factor; D019335:Nitroarginine; D001030:Apamin; D009569:Nitric Oxide; D000001:Calcimycin