Molecular constituents of maxi KCa channels in human coronary smooth muscle: predominant α+β subunit complexes

Tanaka, Yoshio; Meera, Pratap; Song, Min; Knaus, Hans−Günther; Toro, Ligia

doi:10.1111/j.1469-7793.1997.545bj.x

Cited by 235 publications

(233 citation statements)

References 38 publications

(37 reference statements)

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“…This value is somewhat smaller than the one obtained in native tissues (14,17). This difference may be due to the level of expression of the modulatory ␤-subunit (25,42) or of splice variants of Hslo in native cells. The regulatory ␤-subunit is known to modify the biophysical, pharmacological, and modulatory properties of Hslo (31,41,(43)(44)(45).…”

Section: Purified Pkg-i␣ Induces An Increase In the Open Probability contrasting

confidence: 44%

The Large Conductance, Voltage-dependent, and Calcium-sensitive K+ Channel, Hslo, Is a Target of cGMP-dependent Protein Kinase Phosphorylation in Vivo

Alioua¹,

Tanaka²,

Wallner³

et al. 1998

Journal of Biological Chemistry

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164

129

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Native large conductance, voltage-dependent, and Ca 2؉ -sensitive K ؉ channels are activated by cGMP-dependent protein kinase. Two possible mechanisms of kinase action have been proposed: 1) direct phosphorylation of the channel and 2) indirect via PKG-dependent activation of a phosphatase. To scrutinize the first possibility, at the molecular level, we used the human poreforming ␣-subunit of the Ca 2؉ -sensitive K ؉ channel, Hslo, and the ␣-isoform of cGMP-dependent protein kinase I. In cell-attached patches of oocytes co-expressing the Hslo channel and the kinase, 8-Br-cGMP significantly increased the macroscopic currents. This increase in current was due to an increase in the channel voltage sensitivity by ϳ20 mV and was reversed by alkaline phosphatase treatment after patch excision. In inside-out patches, however, the effect of purified kinase was negative in 12 of 13 patches. In contrast, and consistent with the intact cell experiments, purified kinase applied to the cytoplasmic side of reconstituted channels increased their open probability. This stimulatory effect was absent when heat-denatured kinase was used. Biochemical experiments show that the purified kinase incorporates ␥-33 P into the immunopurified Hslo band of ϳ125 kDa. Furthermore, in vivo phosphorylation largely attenuates this labeling in back-phosphorylation experiments. These results demonstrate that the ␣-subunit of large conductance Ca 2؉ -sensitive K ؉ channels is substrate for G-I␣ kinase in vivo and support direct phosphorylation as a mechanism for PKG-I␣-induced activation of maxi-K channels.

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Section: Purified Pkg-i␣ Induces An Increase In the Open Probability contrasting

confidence: 44%

The Large Conductance, Voltage-dependent, and Calcium-sensitive K+ Channel, Hslo, Is a Target of cGMP-dependent Protein Kinase Phosphorylation in Vivo

Alioua¹,

Tanaka²,

Wallner³

et al. 1998

Journal of Biological Chemistry

Self Cite

164

129

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“…These data suggest that in newborn cerebral arteries, intravascular pressure strongly activates 4-AP-sensitive K v channels but only slightly activates K Ca channels. Newborn porcine cerebral artery smooth muscle cells express relatively Ca 2ϩ -insensitive K Ca channels, when compared with K Ca channels in adult arterial smooth muscle cells (42,52,58). The Ca 2ϩ sensitivity of K Ca channels in human coronary artery smooth muscle cells is 4 M at 0 mV (52), and in adult rat arterial smooth muscle cells is 19 M at Ϫ40 mV (42).…”

Section: Pressure-induced Constriction Occurs Via Voltage-dependent Cmentioning

confidence: 99%

“…Newborn porcine cerebral artery smooth muscle cells express relatively Ca 2ϩ -insensitive K Ca channels, when compared with K Ca channels in adult arterial smooth muscle cells (42,52,58). The Ca 2ϩ sensitivity of K Ca channels in human coronary artery smooth muscle cells is 4 M at 0 mV (52), and in adult rat arterial smooth muscle cells is 19 M at Ϫ40 mV (42). In comparison, the K d for Ca 2ϩ of newborn porcine cerebral arteriole smooth muscle cell K Ca channels is 31 M at 0 mV (58).…”

Section: Pressure-induced Constriction Occurs Via Voltage-dependent Cmentioning

confidence: 99%

Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries

Ahmed¹,

Waters²,

Leffler³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries. Am J Physiol Heart Circ Physiol 287: H2061-H2069, 2004. First published July 29, 2004 doi:10.1152/ajpheart.00660.2004.-Mechanisms that underlie autoregulation in the newborn vasculature are unclear. Here we tested the hypothesis that in newborn porcine cerebral arteries intravascular pressure elevates wall tension, leading to an increase in intracellular calcium concentration ([Ca 2ϩ ]i) and a constriction that is opposed by pressure-induced K ϩ channel activation. Incremental step (20 mmHg) elevations in intravascular pressure between 10 and 90 mmHg induced an immediate transient elevation in arterial wall [Ca 2ϩ ]i and a short-lived constriction that was followed by a smaller steady-state [Ca 2ϩ ]i elevation and sustained constriction. Pressures between 10 and 90 mmHg increased steady-state arterial wall [Ca 2ϩ ]i between ϳ142 and 299 nM and myogenic (defined as passive-active) tension between 25 and 437 dyn/cm. The relationship between pressure and myogenic tension was strongly Ca 2ϩ dependent until forced dilation. At low pressure, 60 mM K ϩ induced a steady-state elevation in arterial wall [Ca 2ϩ ]i and a constriction. Nimodipine, a voltage-dependent Ca 2ϩ channel blocker, and removal of extracellular Ca 2ϩ similarly dilated arteries at low or high pressures. 4-Aminopyridine, a voltage-dependent K ϩ (Kv) channel blocker, induced significantly larger constrictions at high pressure, when compared with those at low pressure. Although selective Ca 2ϩ -activated K ϩ (KCa) channel blockers and intracellular Ca 2ϩ release inhibitors induced only small constrictions at low and high pressures, a low concentration of caffeine (1 M), a ryanodine-sensitive Ca 2ϩ release (RyR) channel activator, increased K Ca channel activity and induced dilation. These data suggest that in newborn cerebral arteries, intravascular pressure elevates wall tension, leading to voltage-dependent Ca 2ϩ channel activation, an increase in wall [Ca 2ϩ ]i and Ca 2ϩ -dependent constriction. In addition, pressure strongly activates K v channels that opposes constriction but only weakly activates K Ca channels. wall tension; intravascular pressure; intracellular calcium; voltagedependent potassium channel; calcium-activated potassium channel

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“…The ␤1 subunit contributes to Ca 2ϩ sensitivity of the channel and therefore to regulation of vascular tone. 22,23 However, tempol increased the BK channel I o in mslo only transfected HEK 293 cells. Therefore, the ␤1 subunits may not be essential for activation of BK channels caused by tempol.…”

Section: Upregulation Of Bk Channels In Arteries From Doca-salt Ratsmentioning

confidence: 99%

“…22,23 Upregulation of BK channel ␣ subunit expression and function occurs in VSMC in SHR and aldosterone-salt hypertensive rats, 24 -28 suggesting that there is a dynamic relationship between BP and BK channels. 25,28 Pressure-induced upregulation of BK channel ␣-subunit protein levels and channel function in VSMC provides an important counter-regulatory mechanism to prevent further increases in vascular tone.…”

Section: Upregulation Of Bk Channels In Arteries From Doca-salt Ratsmentioning

confidence: 99%

Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats

Bian

Watts

et al. 2005

Hypertension

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Abstract-Large-conductance Ca 2ϩ -activated potassium (BK) channels modulate vascular smooth muscle tone. Tempol, a superoxide dismutase (SOD) mimetic, lowers blood pressure and inhibits sympathetic nerve activity in normotensive and hypertensive rats. In the present study, we tested the hypotheses depressor responses caused by tempol are partly mediated by vasodilation. It was found that tempol, but not tiron (a superoxide scavenger), dose-dependently relaxed mesenteric arteries (MA) in anesthetized sham and deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Tempol also reduced perfusion pressure in isolated, norepinephrine (NE) preconstricted MA from sham and DOCA-salt hypertensive rats. Maximal responses in DOCA-salt rats were twice as large as those in sham rats. The vasodilation caused by tempol was blocked by iberiotoxin (IBTX, BK channel antagonist, 0.1 mol/L) and tetraethylammonium chloride (TEA) (1 mmol/L). Tempol did not relax KCl preconstricted arteries in sham or DOCA-salt rats, and N -nitro-L-arginine methyl ester (L-NAME), apamin, or glibenclamide did not alter tempol-induced vasodilation. IBTX constricted MA and this response was larger in DOCA-salt compared with sham rats. Western blots and immunohistochemical analysis revealed increased expression of BK channel ␣ subunit protein in DOCA-salt arteries compared with sham arteries. Whole-cell patch clamp studies revealed that tempol enhanced BK channel currents in HEK-293 cells transiently transfected with mslo, the murine BK channel a subunit. These currents were blocked by IBTX. The data indicate that tempol activates BK channels and this effect contributes to depressor responses caused by tempol. Upregulation of the BK channel ␣ subunit contributes to the enhanced depressor response caused by tempol in DOCA-salt hypertension. Ϫ ) increases blood pressure in hypertensive animals and humans in part by reducing the vascular bioavailability of nitric oxide (NO). 1 4-Hydroxy 2,2,6,6,-tetramethyl piperidine 1-oxyl (tempol), a superoxide dismutase (SOD) mimetic, lowers blood pressure in normotensive and hypertensive rats by multiple mechanisms. [2][3][4][5] Acute tempol treatment of normotensive, DOCA-salt and spontaneously hypertensive rats (SHRs) inhibits sympathetic nerve activity and this effect is not prevented by nitric oxide synthase (NOS) inhibition. 2-6 Local application of tempol onto renal sympathetic nerves decreased nerve activity without changing blood pressure (BP) or heart rate (HR). 7 The results suggested that changes in K ϩ channel activity might contribute to sympatho-inhibition caused by tempol. Central administration of tempol in normotensive rats reduced sympathetic nerve discharge 8,9 and attenuated sympathetic excitation caused by central angiotensin II administration. 9 Therefore, it is possible that tempol-induced vasodilation in vivo is masked by its sympatho-inhibitory effects. 9 Chronic tempol treatment attenuates blood pressure increases in hypertensive animals, an effect attributed to improvement in endothelium f...

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Molecular constituents of maxi K_Ca channels in human coronary smooth muscle: predominant α+β subunit complexes

Cited by 235 publications

References 38 publications

The Large Conductance, Voltage-dependent, and Calcium-sensitive K+ Channel, Hslo, Is a Target of cGMP-dependent Protein Kinase Phosphorylation in Vivo

The Large Conductance, Voltage-dependent, and Calcium-sensitive K+ Channel, Hslo, Is a Target of cGMP-dependent Protein Kinase Phosphorylation in Vivo

Ionic mechanisms mediating the myogenic response in newborn porcine cerebral arteries

Activation of Vascular BK Channel by Tempol in DOCA-Salt Hypertensive Rats

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