A Ca(2+)-dependent K+ current is enhanced in arterial membranes of hypertensive rats.

Abstract

This study was designed to investigate the role and regulation of arterial membrane K + channels in hypertension. Aortic segments from normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were suspended for isometric tension recording. In other experiments, proximal aortic segments (PS) (exposed to high pressure) and distal aortic segments (DS) (exposed to lower pressure) were removed from surgically coarcted Sprague-Dawiey rats and similarly prepared. Aortas from SHR and PS dose-dependently contracted to the K + channel blocker tetraethylammonium (TEA) (0.1-10 mM), and this contraction was abolished by preincubation with 0.1 jtM nifedipine. In contrast, the same concentrations of TEA did not contract either WKY or DS aortas. Since block of K + channels by TEA had a different effect on aortic segments exposed to high versus low blood pressure, we compared whole-cell K + currents in isolated vascular cells from the same aortas. The reversal potentials of depolarizationinduced outward currents in WKY, SHR, DS, and PS aortic cells showed a Nernst relation to external K + concentration indicative of selective K + permeability. TEA (1 and 10 mM) was equipotent in blocking these K + currents in patch-clamped cells from all aortic preparations, suggesting that the lack of TEA-induced contractions in WKY and DS aortas was not due to an absence of TEA-sensitive K + channels in these arterial membranes. However, when the Ca 2+ ionophore A23187 (10 /iM) was used to increase the level of cytosolic Ca 2+ in patch-clamped cells, the K + current density in SHR and PS aortic cells was twofold or more higher than in WKY and DS cells. These data suggest that a Ca 2+ -activated, TEA-sensitive K + current is enhanced in aortic muscle cells exposed to high blood pressure. In the intact blood vessel, this may act as a compensatory mechanism to modulate the level of arterial contraction in hypertension. hypothesis that an increased K + permeability regulates arterial reactivity in genetic and experimental rat models of hypertension. In addition, patch-clamp experiments were performed to investigate the ionic channels and cellular mechanisms mediating the enhanced efflux. Our results suggest that a tetraethylammonium chloride (TEA)-sensitive, Ca 2+ -dependent K + current is increased in aortic muscle membranes from hypertensive rats. This K + current appears to be an important modulator of arterial contraction in arteries previously exposed to high blood pressure.Methods Adult (12-16 weeks) Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were obtained from Taconic Farms, Germantown, N.Y. On experimental days, blood pressure was measured by femoral catheterization during pentobarbital anesthesia (45 mg/kg i.p.). Mean arterial pressures (MAP) in WKY and SHR were 98±3 mm Hg and 140±5 mm Hg, respectively. In other experiments, Sprague-Dawiey rats (10 weeks) obtained from Sasco, Madison, Wis., were anesthetized with telazol (40 mg/kg i.m.), and the aorta was partially ligated between the renal art...

Increased barium influx and potassium current in stroke-prone spontaneously hypertensive rats.

“…This increase was detected only at positive membrane potentials and was not observed in the presence of LaCl 3 or TEA" 1 " or in cells in which the internal Ca 2+ level was clamped at zero. Thus, our results are consistent with the findings by Rusch et al, 16 who observed an enhanced whole-cell K + current in aortic smooth muscle cells from SHR after stimulation with the Ca 2+ ionophore A23187. However, we observed an increase in the absence of any pharmacologic intervention.…”

“…These features are consistent with the observation of K + current. Similar to what was reported for vascular smooth muscle K + current, 16 this current reversed at -6 0 ± 2 mV at 5 mmol/L extracellular K + (n=5 to 6), as measured by its tail current. Comparison of the K + current-voltage relations between WKY and SHRSP cells was done by progressively increasing the test potential in 10-mV steps to +80 mV at a constant holding potential of -8 0 mV.…”

“…However, we observed an increase in the absence of any pharmacologic intervention. This discrepancy might be related to differences in animal type (SHRSP versus SHR), cell isolation method, and experimental conditions (eg, inclusion of GTP and ATP in our pipette solution but not in their study 16 In tail artery, Ba 2+ (1 mmol/L) had no effect on resting tension, yet it potentiated 30 mmol/L KCl-induced contraction more in SHRSP than WKY. 29 Based on these observations, we cannot fully exclude the possibility that inhibition of K + channels is involved in potentiating Ba 2+ influx in SHRSP cells.…”

The Chemical Modification of KCa Channels by Carbon Monoxide in Vascular Smooth Muscle Cells

“…DISCUSSION K Ca channels are gated by voltage and calcium and have various conductances and pharmacological sensitivities. The big conductance K Ca channels have been identified in many types of vascular smooth muscle cells (17)(18)(19)(20). The functioning of these K Ca channels controls membrane potential and affects vascular activity.…”

Cardiovascular effects of SCA40, a novel potassium channel opener, in rats

“…They concluded that the activation of Ca2+-activated K+-channels could lead to vasodilatation. Rusch et al (1992) showed that a Ca2'-activated K+-current was enhanced in arterial membranes from genetic and experimental models of hypertensive rats. Asano et al (1993) showed that ChTX-sensitive Ca2+-activated K+-channels were highly activated in arteries from spontaneously hypertensive rats (SHR) as compared to normotensive rats.…”