Ca(2+)‐dependent K+ channels of high conductance in smooth muscle cells isolated from rat cerebral arteries.

Wang, Y; Mathers, David A.

doi:10.1113/jphysiol.1993.sp019567

Cited by 47 publications

(33 citation statements)

References 35 publications

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“…Other reports describe BK currents ranging from hundreds of pA to a few nA [37,38,39,40,41]. It has been noted that these were at less depolarized membrane potentials (40–60 mV) where there may be less BK activation and currents observed here at those membrane potentials are similar to those reported in rat basilar artery, rabbit arcuate artery, mouse colon smooth muscle and human coronary-artery smooth muscle [35,36,37,38,39]. …”

Section: Discussionsupporting

confidence: 73%

“…3c, p > 0.58). The resulting slope factors resemble those reported for cloned dog BK channels expressed in human embryonic kidney cells (15.1 mV, α subunit alone compared to 14–15 mV in this study) [33] and oocytes (11.9–14.1 mV, α + β1 subunits) [34] and do not differ from those observed by other investigators in resistance cerebral arteries from rats (14–16 mV) [35, 36]. Additionally, investigators have found close agreement between the macroscopic methods employed here to determine BK voltage dependency and estimates from single-channel records from the same arterial tissue [11, 34].…”

Section: Discussionsupporting

confidence: 72%

“…These data show that BK channels contain both α and β1 subunits in control and SAH groups. Wang and Mathers [36] tested varying stoichiometries of α:β1 expression and found that each additional β1 subunit contributed a near-linear incremental shift in V 1/2 over a range of 100 mV for α:β1 stoichiometries of 4:0–4:4. The lack of difference between SAH and control cells observed here suggests that there was no downregulation of the β1 subunit after SAH and that both control and vasospastic myocytes express BK channels with an α:β1 stoichiometry of 4:4.…”

Section: Discussionmentioning

confidence: 99%

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Preserved BK Channel Function in Vasospastic Myocytes from a Dog Model of Subarachnoid Hemorrhage

Jahromi

Aihara

et al. 2008

J Vasc Res

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Cerebral vasospasm after subarachnoid hemorrhage (SAH) is due to contraction of smooth muscle cells in the cerebral arteries. The mechanism of this contraction, however, is not well understood. Smooth muscle contraction is regulated in part by membrane potential, which is determined by K⁺ conductance in smooth muscle. Voltage-gated (Kv) and large-conductance, Ca²⁺-activated K⁺ (BK) channels dominate arterial smooth muscle K⁺ conductance. Vasospastic smooth muscle cells are depolarized relative to normal cells, but whether this is due to altered Kv or BK channel function has not been determined. This study determined if BK channels are altered during vasospasm after SAH in dogs. We first characterized BK channels in basilar-artery smooth muscle using whole-cell patch clamping and single-channel recordings. Next, we compared BK channel function between normal and vasospastic cells. There were no significant differences between normal and vasospastic cells in BK current density, kinetics, Ca²⁺ and voltage sensitivity, single-channel conductance or apparent Ca²⁺ affinity. Basilar-artery myocytes had no, small- or intermediate-conductance, Ca²⁺-activated K⁺ channels. The lack of difference in BK channels between vasospastic and control cells suggests alteration(s) in other K⁺ channels or other ionic conductances may underlie the membrane depolarization and vasoconstriction observed during vasospasm after SAH.

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Section: Discussionsupporting

confidence: 73%

Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Preserved BK Channel Function in Vasospastic Myocytes from a Dog Model of Subarachnoid Hemorrhage

Jahromi

Aihara

et al. 2008

J Vasc Res

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“…6), which is consistent with the report that the ACh-activated single channel has a very low open probability in physiological voltage range even with a very high agonist concentration (ACh 500 μM, Inoue et al, 1993). This is not surprising because the single VSMC has a high R input (3-10 GΩ in dispersed VSMCs, Hirst et al, 1989;Wang et al, 1993)). According to Ohm's law, a 2 pA current should roughly cause a 6-20 mV depolarization in cells of 3-10 GΩ, which is about the size of ACh-depolarization from intracellular recordings (Figs.…”

Section: Technical Issuessupporting

confidence: 79%

ACh-induced depolarization in inner ear artery is generated by activation of a TRP-like non-selective cation conductance and inactivation of a potassium conductance

et al. 2008

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Adequate cochlear blood supply by the spiral modiolar artery (SMA) is critical for normal hearing. ACh may play a role in neuroregulation of the SMA but several key issues including its membrane action mechanisms remain poorly understood. Besides its well-known endothelium-dependent hyperpolarizing action, ACh can induce a depolarization in vascular cells. Using intracellular and whole-cell recording techniques on cells in guinea pig in vitro SMA, we studied the ionic mechanism underlying the ACh-depolarization and found that: 1) ACh induced a DAMP-sensitive depolarization when intermediate conductance K Ca channels were blocked by charybdotoxin or nitrendipine. The ACh-depolarization was associated with a decrease in input resistance (R input ) in high membrane potential (V m ) (~−40 mV) cells but with no change or an increase in R input in low V m (~−75 mV) cells. ACh-depolarization was attenuated by background membrane depolarization from ~−70 mV in the majority of cells; 2) ACh-induced inward current in smooth muscle cells embedded in a SMA segment often showed a U-shaped I/V curve, the reversal potential of its two arms being near E K and 0 mV respectively; 3) ACh-depolarization was reduced by low Na + , zero K + or 20 mM K + bath solutions; 4) ACh-depolarization was inhibited by La 3+ in all cells tested, by 4-AP and flufenamic acid in low V m cells, but was not sensitive to Cd 2+ , Ni 2+ , nifedipine, niflumic acid, DIDS, IAA94, linopirdine or amiloride. We conclude that ACh-induced vascular depolarization was generated mainly by activation of a TRP-like non-selective cation channel and by inactivation of an inward rectifier K + channel.

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“…Recently, it is reported that internally applied TEA blocks the Ca-dependent K+ channels with high sen sitivity (14), suggesting a difference in the internal pore (15) of the channels in rat cerebral artery compared with other tissues. Thus, the internal binding site for TAAs in the KATP channels in vascular smooth muscles seems differ ent from that in cardiac or skeletal muscles.…”

mentioning

confidence: 99%

A Possibility That the ATP-Sensitive Potassium Channel in Coronary Artery Has a High-Affinity Internal Binding Site for Tetraalkylammonium

Orito

Yanagisawa

Taira

1994

Japanese Journal of Pharmacology

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ABSTRACT-The functionally responsible sites for the blocking action of tetraalkylammonium ions (TAAs) in ATP-sensitive K+ (KATP) channels opened by levcromakalim were estimated in canine coronary artery. Tetraethylammonium (TEA) and tetrabutylammonium (TBA) inhibited the levcromakalim-induced relaxation in a noncompetitive manner. Analyses of the noncompetitive antagonism revealed that the bind ing constant of TBA was about 900 times lower than that of TEA, although the reported affinity of TBA for the internal binding site in various K+ channels was only 10 times higher than that of TEA. TBA is much more lipid-soluble and permeable through membranes than TEA. Thus, TBA blocks KATP channels by bind ing to a possible high-affinity internal site for TAAs, whereas TEA seems to bind to the external site.Keywords: ATP-sensitive K+ (KATP) channel, Levcromakalim, Tetraalkylammonium ion Symmetric tetraalkylammonium ions (TAAs) are fre quently used K+ channel blockers. 86Rb+ efflux through ATP-sensitive K+ (KATP) channels stimulated by cromakalim was inhibited by extracellularly applied TAAs in rat aorta, and the inhibitory potency of TAAs increased as the alkyl chain length was increased from methyl to pentyl (1). Thus, lipophilicity of TAAs seems to play an important role in their ability to block KATP chan nels. Because the permeability through membranes de pends mainly on their lipophilicity, it is likely that TAAs act on the internal binding site in the KATP channel. Re cently, however, it has been reported that there are two (external and internal) binding sites for TAAs in the pore forming region of various cloned K+ channels (2-4). The differential blocking potency of TAAs might be due to the different affinities to the two binding sites for TAAs in the KATP channel. We examined the antagonism of two TAAs, tetraethylammonium (TEA) and tetrabutylammo nium (TBA), that have different lipophilicity and permeability through membranes against relaxation in duced by the specific KATP channel opener levcromakalim (5, 6) and explored the binding sites for TAAs in KATP channels in canine coronary artery.Circumflex coronary arteries were obtained from 16 mongrel dogs of either sex, weighing 9-12 kg, anesthe tized with sodium pentobarbital (30 mg/kg, i.v.). The coronary arteries isolated from the hearts were cut into 3 to 4-mm-long ring segments. The intimal surface of the ring segments was gently rubbed to remove the endothelium. Each ring was suspended in a 25-ml organ bath contain ing modified Krebs solution of the following composi tion: 119 mM NaCI, 4.7 mM KCI, 1.17 mM MgSO4, 25 mM NaHCO3, 1.18 mM KH2PO4, 2.5 mM CaC12 and 11 mM glucose at 37C, aerated with 95% 02 and 5016 C02. Changes in the force of contraction were measured by force transducers. After a 1.5-hr equilibration with a load of 20 mN, the arterial rings were exposed to TEA or TBA and then contracted by addition of KCl to normal solu tion to make a final concentration of 25 mM KC1. After the increased force of contraction had reached a plateau about 1.5 2 hr...

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Ca(2+)‐dependent K+ channels of high conductance in smooth muscle cells isolated from rat cerebral arteries.

Cited by 47 publications

References 35 publications

Preserved BK Channel Function in Vasospastic Myocytes from a Dog Model of Subarachnoid Hemorrhage

Preserved BK Channel Function in Vasospastic Myocytes from a Dog Model of Subarachnoid Hemorrhage

ACh-induced depolarization in inner ear artery is generated by activation of a TRP-like non-selective cation conductance and inactivation of a potassium conductance

A Possibility That the ATP-Sensitive Potassium Channel in Coronary Artery Has a High-Affinity Internal Binding Site for Tetraalkylammonium

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