Pressure-induced activation of membrane K+ current in rat saphenous artery.

Abstract

Pressurization of isolated arteries may result in Ca 2+-dependent contraction and membrane depolarization. Because the open state probability of some vascular muscle K + channels is augmented by rises in cytosolic Ca 2+ and membrane depolarization, we investigated the possibility that increases in intraluminal pressure activate K + channels in isolated, perfused rat saphenous arteries. Stepwise increases in intraluminal pressure from 5 to 205 mm Hg resulted in increasing, active arterial contraction, measured as smaller diameters in physiological salt solution than in Ca 2+ -free solution. Addition of 10 mM tetraethylammonium to the physiological salt solution to block arterial muscle K + channels caused progressively greater diameter reductions at pressures above 25 mm Hg. Microelectrode measurements of membrane potential showed that tetraethylammonium depolarized arterial muscle more at 105 mm Hg (16±1 mV) than at 25 mm Hg (10±l mV). The sensitivity of K + current to tetraethylammonium was also demonstrated in patch-clamped vascular muscle cells from the same arteries. Peak whole-cell K + current was suppressed 47% and 79% by 1 and 10 mM tetraethylammonium, respectively. This same current was enhanced 3.6-fold by the Ca 2+ ionophore A23187 (10 /iM), suggesting a Ca 2+ dependence. We conclude that increases in intraluminal pressure progressively activate tetraethylammonium-sensitive K + channels in the arterial muscle membrane. This can serve as a negative feedback mechanism to limit pressure-induced arterial constriction. (Hypertension 1992;19:725-729) KEY WORDS • vascular smooth muscle • tetraethylammonium compounds • blood pressure • calcium • potassium channels P ressure-induced contraction of arterial muscle minimizes arterial diameter changes during local blood pressure alterations. Many studies have focused on the mechanisms for Ca 2+ activation of arterial muscle in this response, as Ca 2+ influx appears to be required for myogenic activation.1 -4 However, the final level of arterial muscle contraction in response to changes in intraluminal pressure (IP) likely reflects the integrated reaction of multiple membrane ionic mechanisms. Of these, the function of arterial membrane K + channels has received scant attention, despite their recognized role as key modulators of arterial contraction and excitability. 5In view of this, the purpose of this study was to test the hypothesis that arterial membrane K + channels buffer the pressure-induced contraction of arterial muscle segments. Using tetraethylammonium (TEA) to block vascular muscle K + channels in perfused rat saphenous arteries, we estimated the contribution of K + current to arterial diameter and membrane potential (E m ) at IP values from 5 to 205 mm Hg. We used patch-clamp methods to document K + current sensitivity to TEA-induced block and to increases of cytosolic Ca 2+ in isolated arterial cells. The results suggest that activation of membrane K + channels may be a mechanism for attenuation of acute pressure-induced constriction in small arte...

Characterization of the large-conductance Ca-activated K channel in myocytes of rat saphenous artery

“…4A, which illustrates a typical family of outward K currents from dialysed myocytes evoked by 400-ms depolarizing pulses from a holding potential of -60 mV, with a physiological K gradient ([K] i 140 mM; [K] o 5 mM) and low [Ca 2+ ] i (10 -8 M). In the lower range of potentials examined (≤+40 mV), the outward currents did not exceed a few hundred picoamperes, in accordance with other studies of vascular myocytes [3,7,13]. At these potentials the DRK and A current components are maximally activated, thus the maximal whole-cell contribution of these components must be less than 10 nS in rat saphenous myocytes.…”

“…We elected to use this artery because it has the histological characteristics of an arteriole (thus representing a major determinant of peripheral resistance and hence arterial blood pressure), but has sufficient mass to give a viable yield of isolated myocytes. The presence of significant BK current in this tissue has been reported [3]. However, to our knowledge, a comprehensive characterization of its gating behavior and pharmacological profile, both important aspects in understanding its functional relevance, remains to be carried out.…”

Endothelium‐dependent relaxations in sheep pulmonary arteries and veins: resistance to block by NG‐nitro‐L‐arginine in pulmonary hypertension

“…This phenomenon was not specifically related to a reduction in NO synthesis, because endothelium-dependent relaxation was not impaired in the air embolization model of pulmonary hypertension, but it could have been related to the elevation of pulmonary pressures, hypoxaemia or the inflammatory response. A putative role for elevated pressure in the appearance of L-NOARG resistance and upregulation ofK+ channels in short-term and chronic pulmonary hypertensive arteries is consistent with the observation that L-NOARG resistance exists constitutively in the high pressure systemic vasculature (Cowan et al, 1993;Kilpatrick & Cocks, 1994) (Berezi et al, 1992;Brayden & Nelson, 1992). Elevated pressure, however, is unlikely to be the sole factor involved in the upregulation of the K+ channel-mediated system, because L-NOARG resistance was observed in veins from short-term pulmonary hypertensive sheep in which left atrial pressure (and thus pulmonary venous pressure) was decreased.…”

Mechanotransduction by Vascular Smooth Muscle

“…Using a combination of patch clamp techniques (excised inside-out patch) and isolated, pressu rized rat cerebral arteries, Brayden and Nelson [93] showed that the degree of myogenic tone was regulated in part by the activation of large-conductance calcium-acti vated potassium channels (Kca) in arterial smooth mus cle. Pressure-induced activation of membrane potassium current in the rat saphenous artery was reported at the same time (1992) by Berczi et al [94] and also porposed as a potential feedback mechanism for myogenic constric tion.…”