Single-channel and functional characteristics of a KCa channel in vascular muscle membranes of human saphenous veins.
The saphenous vein is used extensively to test for the effects of vasodilator substances on venous reactivity, but the K+ channel types that mediate vasodilation have not been identified. Thus the goal of this study was to identify K+ channel types in vascular smooth muscle membranes of human saphenous vein (HSV), which may contribute to membrane repolarization and control of venous tone. Fourteen HSVs obtained from bypass surgery were enzymatically dissociated into single vascular myocytes for patch-clamp analysis of inside-out patches (n = 81). HSV membranes showed primarily high-conductance (226 pS) K+ channels, which accounted for > or = 95% of total patch current at physiologic voltages. Channels were highly K+ selective, showed steep voltage and Ca2+ sensitivity, and were blocked by 100 nM iberiotoxin and < or = 1 mM tetraethylammonium (TEA). These Ca(2+)-sensitive channels (KCa) also showed stacked openings in depolarized patches exposed to 300-1,000 nM calcium, suggesting multiple functional KCa channels in a single membrane patch. In tension-recording studies, isolated segments of HSV exposed to 100 nM norepinephrine contracted further during progressive block of KCa channels by 0.1-3 mM TEA, suggesting that KCa channels are pathways for repolarization and vasodilation in HSV smooth muscle cells. Our finding of KCa channels in smooth muscle membranes of HSV, if extended to the plasma membranes of other human peripheral veins, suggests that this channel may represent a therapeutic site for alleviation of conditions of increased venous tone.
Zhang
H
H
Department of Physiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Li
P
P
Almassi
G H
GH
Nicolosi
A
A
Olinger
G N
GN
Rusch
N J
NJ
D000328:Adult; D000368:Aged; D002118:Calcium / Q000494:pharmacology*; D004563:Electrochemistry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D012501:Saphenous Vein / Q000187:drug effects / Q000502:physiology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D014662:Vasoconstrictor Agents; D019789:Tetraethylammonium; D002118:Calcium; D009638:Norepinephrine