Comparison of K+ channel properties in freshly isolated myocytes from thoracic aorta of WKY and SHR.
Altered function of smooth muscle cell K+ channels have been reported in hypertension, but the contribution of various K+ channel types to these changes has not been completely determined. The purpose of this study was to compare the contribution of K+ channel types to whole cell K+ currents recorded from isolated thoracic aorta myocytes of 13 to 15 week old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Cells were isolated by collagenase and elastase digestion, and K+ currents recorded using whole cell voltage clamp methods at room temperature. Cells were superfused with a solution containing (in mmol/ L) 140 NaCl, 5 KCl, 2 CaCl2, 1 MgCl2, 10 HEPES, and 10 glucose. Pipettes were filled with a solution containing (in mmol/L) 120 KCl, 5 NaCl, 5 MgATP, 20 HEPES, and 10 BAPTA. The K+ currents (IK) recorded from a holding potential (HP) of -80 mV were smaller in the SHR compared to those in WKY (for example, at 20 mV: WKY = 6.1 +/- 0.6 pA/pF and SHR = 3.7 +/- 0.2 pA/pF). Values of cell capacitance were not different between the two groups (WKY = 25.2 +/- 3.2 pF and SHR = 26.6 +/- 1.9 pF). A component of IK inhibited by voltage (Kv) over the range from -80 to -20 mV was smaller in SHR. The voltage dependence of Kv availability and activation were not significantly different between the two groups. IK recorded from a HP = -20 mV (KCa) was not different between the two groups. Difference currents calculated from IK measured at HP of -80 and -20 mV (that is, Kv) were smaller in SHR as was the fraction of IK inhibited by 4-aminopyridine. These results suggest that under conditions of low intracellular [Ca2+] there are no differences in KCa currents, but the Kv currents are smaller in SHR. Inhibition of Kv by 4-aminopyridine (0.1 to 10 mmol/L) caused larger increases in basal tone in WKY aorta. These results suggest that Kv channels contribute to resting K+ conductance in both WKY and SHR aorta, but with a relatively larger contribution in the WKY.
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Bockus Research Institute, Graduate Hospital, Philadelphia, PA 19146.
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques; D010455:Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry* / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012604:Scorpion Venoms / Q000494:pharmacology
D010455:Peptides; D015221:Potassium Channels; D012604:Scorpion Venoms; C064719:iberiotoxin; D015761:4-Aminopyridine