Histamine-induced depolarization: ionic mechanisms and role in sustained contraction of rabbit cerebral arteries

2000 ◽  
Vol 278 (6) ◽  
pp. H2094-H2104 ◽  
Author(s):  
N. I. Gokina ◽  
J. A. Bevan
Keyword(s):  
Isometric Force ◽  
Cerebral Arteries ◽  
Cation Channels ◽  
Sustained Contraction ◽  
Nonselective Cation Channels ◽  
High K ◽  
Voltage Dependent ◽  
Ionic Mechanisms ◽  
A Minor

The role of membrane depolarization in the histamine-induced contraction of the rabbit middle cerebral artery was examined by simultaneous measurements of membrane potential and isometric force. Histamine (1–100 μM) induced a concentration-dependent sustained contraction associated with sustained depolarization. Action potentials were observed during depolarization caused by histamine but not by high-K+ solution. K+-induced contraction was much smaller than sustained contraction associated with the same depolarization caused by histamine. Nifedipine attenuates histamine-induced sustained contraction by 80%, with no effect on depolarization. Inhibition of nonselective cation channels with Co2+ (100–200 μM) reversed the histamine-induced depolarization and relaxed the arteries but induced only a minor change in K+-induced contraction. In the presence of Co2+ and in low-Na+solution, histamine-evoked depolarization and contraction were transient. We conclude that nonselective cation channels contribute to histamine-induced sustained depolarization, which stimulates Ca2+ influx through voltage-dependent Ca2+channels participating in contraction. The histamine-induced depolarization, although an important and necessary mechanism, cannot fully account for sustained contraction, which may be due in part to augmentation of currents through voltage-dependent Ca2+channels and Ca2+ sensitization of the contractile process.

Nuciferine Relaxes Tracheal Rings via the Blockade of VDLCC and NSCC Channels

Planta Medica ◽  
2017 ◽  
Vol 84 (02) ◽  
pp. 83-90 ◽  
Author(s):  
Xiao Yang ◽  
Meng-Fei Yu ◽  
Jun Lei ◽  
Yong-Bo Peng ◽  
Ping Zhao ◽  
...  
Keyword(s):  
Muscle Tone ◽  
Smooth Muscles ◽  
Cation Channels ◽  
Dependent Manner ◽  
Aporphine Alkaloid ◽  
Nonselective Cation Channels ◽  
High K ◽  
Voltage Dependent ◽  
Resting Muscle ◽  
Dose Dependent

AbstractThis study aimed to elucidate the mechanisms of nuciferine (a main aporphine alkaloid of lotus leaf extract), which can induce relaxation in contracted tracheal rings. Under Ca2+-free and 2 mM Ca2+ conditions, we found that nuciferine had no effect on the resting muscle tone of tracheal rings. In contrast, nuciferine relaxed high K+-contracted mouse tracheal rings in a dose-dependent manner and inhibited both Ca2+ influx and voltage-dependent L-type Ca2+ channel currents induced by high K+. Similarly, nuciferine also inhibited acetylcholine-induced contractions in mouse tracheal rings in a dose-dependent manner. Meanwhile, both acetylcholine-induced intracellular Ca2+ influx and whole-cell currents of nonselective cation channels were blocked by nuciferine. Together, the results indicate that nuciferine-induced relaxation in tracheal rings mainly occurred due to the inhibition of extracellular Ca2+ influx through the blockade of voltage-dependent L-type Ca2+ channels and/or nonselective cation channels. These results suggest that nuciferine has a therapeutic effect on respiratory diseases associated with the aberrant contraction of airway smooth muscles and/or bronchospasm.

scholarly journals Role of intracellular Ca2+ release in histamine-induced depolarization in rabbit middle cerebral artery

2000 ◽  
Vol 278 (6) ◽  
pp. H2105-H2114 ◽  
Author(s):  
N. I. Gokina ◽  
J. A. Bevan
Keyword(s):  
Membrane Potential ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Isometric Force ◽  
Niflumic Acid ◽  
Cation Channels ◽  
Free Solution ◽  
Nonselective Cation Channels

The role of Ca2+ mobilization from intracellular stores and Ca2+-activated Cl− channels in caffeine- and histamine-induced depolarization and contraction of the rabbit middle cerebral artery has been studied by recording membrane potential and isometric force. Caffeine induced a transient contraction and a transient followed by sustained depolarization. The transient depolarization was abolished by ryanodine, DIDS, and niflumic acid, suggesting involvement of Ca2+-activated Cl− channels. Histamine-evoked transient contraction in Ca2+-free solution was abolished by ryanodine or by caffeine-induced depletion of Ca2+ stores. Ryanodine slowed the development of depolarization induced by histamine in Ca2+-containing solution but did not affect its magnitude. In arteries treated with 1 mM Co2+, histamine elicited a transient depolarization and contraction, which was abolished by ryanodine. DIDS and niflumic acid reduced histamine-evoked depolarization and contraction. Histamine caused a sustained depolarization and contraction in low-Cl− solution. These results suggest that Ca2+ mobilization from ryanodine-sensitive stores is involved in histamine-induced initial, but not sustained, depolarization and contraction. Ca2+-activated Cl− channels contribute mainly to histamine-induced initial depolarization and less importantly to sustained depolarization, which is most likely dependent on activation of nonselective cation channels.

Functional heterogeneity of endothelial P2 purinoceptors in the cerebrovascular tree of the rat

1999 ◽  
Vol 277 (3) ◽  
pp. H893-H900 ◽  
Author(s):  
Junping You ◽  
T. David Johnson ◽  
Sean P. Marrelli ◽  
Robert M. Bryan
Keyword(s):  
Cerebral Arteries ◽  
No Synthase ◽  
Third Order ◽  
Selective Agonist ◽  
Middle Cerebral Arteries ◽  
Spontaneous Tone ◽  
A Minor ◽  
Calcium Activated Potassium Channel ◽  
Dose Dependent

The effects of stimulating P2Y1 or P2Y2 purinoceptors on the endothelium of isolated middle cerebral arteries (MCAs), third-order branches of the MCA (bMCAs), and penetrating arterioles (PAs) of the rat were studied. After pressurization and development of spontaneous tone (25% contraction), resting diameters for MCAs, bMCAs, and PAs were 203 ± 5 ( n = 50), 99 ± 2 ( n = 42), and 87 ± 2 μm ( n = 53), respectively. Luminal application of the P2Y1-selective agonist 2-methylthioadenosine 5′-triphosphate elicited dose-dependent dilations (or loss of intrinsic tone) in MCAs but not in bMCAs or PAs. The dilation in MCAs was completely blocked by removal of the endothelium or by nitro-l-arginine methyl ester (10−5 M), an inhibitor of NO synthase. Luminal application of the P2Y2-selective agonist ATP elicited dilations in MCAs, bMCAs, and PAs. Removal of the endothelium abolished the dilations in all vessel groups. Dilations in MCAs have been shown to involve both NO and endothelium-derived hyperpolarizing factor (EDHF). The dilations in bMCAs and PAs had a minor NO component and prominent EDHF component; that is, 1) the dilations to ATP were not diminished by the combined inhibition of NO synthase and cyclooxygenase, 2) the dilations were accompanied by significant hyperpolarizations of the vascular smooth muscle (∼15 mV), and 3) the dilations were completely abolished by the calcium-activated potassium channel blocker charybdotoxin. We concluded that the role of NO in purinoceptor-induced dilations diminishes along the cerebrovascular tree in the rat, whereas the role of EDHF becomes more prominent.

Hormone-induced rise in cytosolic Ca2+ in axolotl hepatocytes: properties of the Ca2+ influx channel

1997 ◽  
Vol 273 (5) ◽  
pp. C1526-C1532 ◽  
Author(s):  
Thomas Lenz ◽  
Jochen W. Kleineke
Keyword(s):  
Inhibitory Concentration ◽  
Cation Channels ◽  
Strong Inhibition ◽  
Michaelis Constant ◽  
Cyclic Monophosphate ◽  
First Order ◽  
First Order Kinetics ◽  
Nonselective Cation Channels ◽  
Store Depletion ◽  
Voltage Dependent

Calcium entry in nonexcitable cells occurs through Ca2+-selective channels activated secondarily to store depletion and/or through receptor- or second messenger-operated channels. In amphibian liver, hormones that stimulate the production of adenosine 3′,5′-cyclic monophosphate (cAMP) also regulate the opening of an ion gate in the plasma membrane, which allows a noncapacitative inflow of Ca2+. To characterize this Ca2+ channel, we studied the effects of inhibitors of voltage-dependent Ca2+ channels and of nonselective cation channels on 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP)-dependent Ca2+ entry in single axolotl hepatocytes. Ca2+ entry provoked by 8-BrcAMP in the presence of physiological Ca2+ followed first-order kinetics (apparent Michaelis constant = 43 μM at the cell surface). Maximal values of cytosolic Ca2+ (increment ∼300%) were reached within 15 s, and the effect was transient (half time of 56 s). We report a strong inhibition of cAMP-dependent Ca2+ entry by nifedipine [half-maximal inhibitory concentration (IC50) = 0.8 μM], by verapamil (IC50 = 22 μM), and by SK&F-96365 (IC50 = 1.8 μM). Depolarizing concentrations of K+were without effect. Gadolinium and the anti-inflammatory compound niflumate, both inhibitors of nonselective cation channels, suppressed Ca2+ influx. This “profile” indicates a novel mechanism of Ca2+ entry in nonexcitable cells.

Effects of Ca2+ channel antagonists on nerve stimulation-induced and ischemia-induced myocardial interstitial acetylcholine release in cats

2006 ◽  
Vol 291 (5) ◽  
pp. H2187-H2191 ◽  
Author(s):  
Toru Kawada ◽  
Toji Yamazaki ◽  
Tsuyoshi Akiyama ◽  
Kazunori Uemura ◽  
Atsunori Kamiya ◽  
...  
Keyword(s):  
Nerve Stimulation ◽  
Acetylcholine Release ◽  
Local Administration ◽  
Ach Release ◽  
Parasympathetic Nerve ◽  
Nonselective Cation Channels ◽  
Voltage Dependent ◽  
Stretch Activated Channels ◽  
Postganglionic Nerve

Although an axoplasmic Ca2+ increase is associated with an exocytotic acetylcholine (ACh) release from the parasympathetic postganglionic nerve endings, the role of voltage-dependent Ca2+ channels in ACh release in the mammalian cardiac parasympathetic nerve is not clearly understood. Using a cardiac microdialysis technique, we examined the effects of Ca2+ channel antagonists on vagal nerve stimulation- and ischemia-induced myocardial interstitial ACh releases in anesthetized cats. The vagal stimulation-induced ACh release [22.4 nM (SD 10.6), n = 7] was significantly attenuated by local administration of an N-type Ca2+ channel antagonist ω-conotoxin GVIA [11.7 nM (SD 5.8), n = 7, P = 0.0054], or a P/Q-type Ca2+ channel antagonist ω-conotoxin MVIIC [3.8 nM (SD 2.3), n = 6, P = 0.0002] but not by local administration of an L-type Ca2+ channel antagonist verapamil [23.5 nM (SD 6.0), n = 5, P = 0.758]. The ischemia-induced myocardial interstitial ACh release [15.0 nM (SD 8.3), n = 8] was not attenuated by local administration of the L-, N-, or P/Q-type Ca2+ channel antagonists, by inhibition of Na+/Ca2+ exchange, or by blockade of inositol 1,4,5-trisphosphate [Ins( 1 , 4 , 5 )P3] receptor but was significantly suppressed by local administration of gadolinium [2.8 nM (SD 2.6), n = 6, P = 0.0283]. In conclusion, stimulation-induced ACh release from the cardiac postganglionic nerves depends on the N- and P/Q-type Ca2+ channels (with a dominance of P/Q-type) but probably not on the L-type Ca2+ channels in cats. In contrast, ischemia-induced ACh release depends on nonselective cation channels or cation-selective stretch activated channels but not on L-, N-, or P/Q type Ca2+ channels, Na+/Ca2+ exchange, or Ins( 1 , 4 , 5 )P3 receptor-mediated pathway.

Alkaline pH shifts Ca2+ sparks to Ca2+waves in smooth muscle cells of pressurized cerebral arteries

2002 ◽  
Vol 283 (6) ◽  
pp. H2169-H2176 ◽  
Author(s):  
Thomas J. Heppner ◽  
Adrian D. Bonev ◽  
L. Fernando Santana ◽  
Mark T. Nelson
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cerebral Arteries ◽  
Ryanodine Receptors ◽  
Muscle Cells ◽  
Alkaline Ph ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
A Minor ◽  
External Ph

The effects of external pH (7.0–8.0) on intracellular Ca2+ signals (Ca2+ sparks and Ca2+ waves) were examined in smooth muscle cells from intact pressurized arteries from rats. Elevating the external pH from 7.4 to 7.5 increased the frequency of local, Ca2+transients, or “Ca2+ sparks,” and, at pH 7.6, significantly increased the frequency of Ca2+ waves. Alkaline pH-induced Ca2+ waves were inhibited by blocking Ca2+ release from ryanodine receptors but were not prevented by inhibitors of voltage-dependent Ca2+ channels, phospholipase C, or inositol 1,4,5-trisphosphate receptors. Activating ryanodine receptors with caffeine (5 mM) at pH 7.4 also induced repetitive Ca2+ waves. Alkalization from pH 7.4 to pH 7.8–8.0 induced a rapid and large vasoconstriction. Approximately 82% of the alkaline pH-induced vasoconstriction was reversed by inhibitors of voltage-dependent Ca2+ channels. The remaining constriction was reversed by inhibition of ryanodine receptors. These findings indicate that alkaline pH-induced Ca2+ waves originate from ryanodine receptors and make a minor, direct contribution to alkaline pH-induced vasoconstriction.

Effect of acidosis on tension and [Ca2+]iin rat cerebral arteries: is there a role for membrane potential?

1998 ◽  
Vol 274 (2) ◽  
pp. H655-H662 ◽  
Author(s):  
Hong-Li Peng ◽  
Peter E. Jensen ◽  
Holger Nilsson ◽  
Christian Aalkjær
Keyword(s):  
Smooth Muscle ◽  
Membrane Potential ◽  
Isometric Force ◽  
Cerebral Arteries ◽  
Bathing Solution ◽  
Hypercapnic Acidosis ◽  
Small Arteries ◽  
Intracellular Ca ◽  
Intracellular Microelectrodes

The cellular mechanism responsible for the reduction of tension in cerebral small arteries to acidosis is not known. In this study the role of smooth muscle intracellular Ca2+ concentration ([Ca2+]i) and membrane potential for the relaxation to acidosis was investigated in isolated rat cerebral small arteries. Isometric force was measured simultaneously with [Ca2+]i(fura 2) or with membrane potential (intracellular microelectrodes), and acidosis was induced by increasing[Formula: see text] or reducing[Formula: see text] of the bathing solution. Both hypercapnic and normocapnic acidosis were associated with a reduction of intracellular pH [measured with 2′,7′-bis-(carboxyethyl)-5 (and -6)-carboxyfluorescein], caused relaxation, and reduced [Ca2+]i. However, whereas hypercapnic acidosis caused hyperpolarization, normocapnic acidosis was associated with depolarization. It is concluded that a reduction of [Ca2+]iis in part responsible for the direct effect of the acidosis on the vascular smooth muscle both during normo- and hypercapnia. The mechanism responsible for the reduction of [Ca2+]idiffers between the hypercapnic and normocapnic acidosis, being partly explained by hyperpolarization during hypercapnic acidosis, whereas it is seen despite depolarization during normocapnic acidosis.

scholarly journals Role of nonselective cation channels in spontaneous and protein kinase A-stimulated calcium signaling in pituitary cells

2011 ◽  
Vol 301 (2) ◽  
pp. E370-E379 ◽  
Author(s):  
Melanija Tomić ◽  
Marek Kucka ◽  
Karla Kretschmannova ◽  
Shuo Li ◽  
Maria Nesterova ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Electrical Activity ◽  
Calcium Signaling ◽  
Calcium Influx ◽  
Cation Channels ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Nonselective Cation Channels ◽  
In Cells

Several receptors linked to the adenylyl cyclase signaling pathway stimulate electrical activity and calcium influx in endocrine pituitary cells, and a role for an unidentified sodium-conducting channel in this process has been proposed. Here we show that forskolin dose-dependently increases cAMP production and facilitates calcium influx in about 30% of rat and mouse pituitary cells at its maximal concentration. The stimulatory effect of forskolin on calcium influx was lost in cells with inhibited PKA (cAMP-dependent protein kinase) and in cells that were haploinsufficient for the main PKA regulatory subunit but was preserved in cells that were also haploinsufficient for the main PKA catalytic subunit. Spontaneous and forskolin-stimulated calcium influx was present in cells with inhibited voltage-gated sodium and hyperpolarization-activated cation channels but not in cells bathed in medium, in which sodium was replaced with organic cations. Consistent with the role of sodium-conducting nonselective cation channels in PKA-stimulated Ca2+ influx, cAMP induced a slowly developing current with a reversal potential of about 0 mV. Two TRP (transient receptor potential) channel blockers, SKF96365 and 2-APB, as well as flufenamic acid, an inhibitor of nonselective cation channels, also inhibited spontaneous and forskolin-stimulated electrical activity and calcium influx. Quantitative RT-PCR analysis indicated the expression of mRNA transcripts for TRPC1 >> TRPC6 > TRPC4 > TRPC5 > TRPC3 in rat pituitary cells. These experiments suggest that in pituitary cells constitutively active cation channels are stimulated further by PKA and contribute to calcium signaling indirectly by controlling the pacemaking depolarization in a sodium-dependent manner and directly by conducting calcium.

Ionic mechanisms underlying electrical slow waves in canine airway smooth muscle

1998 ◽  
Vol 275 (3) ◽  
pp. L516-L523 ◽  
Author(s):  
Luke J. Janssen ◽  
Chris Hague ◽  
Roopung Nana
Keyword(s):  
Smooth Muscle ◽  
Channel Blocker ◽  
Niflumic Acid ◽  
Slow Waves ◽  
Bronchial Smooth Muscle ◽  
High K ◽  
Voltage Dependent ◽  
Ionic Mechanisms ◽  
Opening And Closing ◽  
External K

In canine bronchial smooth muscle (BSM), spasmogens evoke oscillations in membrane potential (“slow waves”). The depolarizing phase of the slow waves is mediated by voltage-dependent Ca2+ channels; we examined the roles played by Cl− and K+ currents and Na+-K+-ATPase activity in mediating the repolarizing phase. Slow waves were evoked using tetraethylammonium (25 mM) in the presence or absence of niflumic acid (100 μM; Cl− channel blocker) or ouabain (10 μM; block Na+-K+-ATPase) or after elevating external K+concentration ([K+]) to 36 mM (to block K+ currents); curve fitting was performed to quantitate the rates of rise/fall and frequency under these conditions. Slow waves were markedly slowed, and eventually abolished, by niflumic acid but were unaffected by ouabain or high [K+]. Electrically evoked slow waves were also blocked in similar fashion by niflumic acid. We conclude that the repolarization phase is mediated by Ca2+-dependent Cl− currents. This information, together with our earlier finding that the depolarizing phase is due to voltage-dependent Ca2+ current, suggests that slow waves in canine BSM involve alternating opening and closing of Ca2+ and Cl− channels.

scholarly journals KIR channels tune electrical communication in cerebral arteries

2016 ◽  
Vol 37 (6) ◽  
pp. 2171-2184 ◽  
Author(s):  
Maria Sancho ◽  
Nina C Samson ◽  
Bjorn O Hald ◽  
Ahmed M Hashad ◽  
Sean P Marrelli ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
Arterial Wall ◽  
Cerebral Arteries ◽  
Pcr Analysis ◽  
Vasomotor Response ◽  
Rightward Shift ◽  
Voltage Dependent

The conducted vasomotor response reflects electrical communication in the arterial wall and the distance signals spread is regulated by three factors including resident ion channels. This study defined the role of inward-rectifying K+ channels (KIR) in governing electrical communication along hamster cerebral arteries. Focal KCl application induced a vasoconstriction that conducted robustly, indicative of electrical communication among cells. Inhibiting dominant K+ conductances had no attenuating effect, the exception being Ba2+ blockade of KIR. Electrophysiology and Q-PCR analysis of smooth muscle cells revealed a Ba2+-sensitive KIR current comprised of KIR2.1/2.2 subunits. This current was surprisingly small and when incorporated into a model, failed to account for the observed changes in conduction. We theorized a second population of KIR channels exist and consistent with this idea, a robust Ba2+-sensitive KIR2.1/2.2 current was observed in endothelial cells. When both KIR currents were incorporated into, and then inhibited in our model, conduction decay was substantive, aligning with experiments. Enhanced decay was ascribed to the rightward shift in membrane potential and the increased feedback arising from voltage-dependent-K+ channels. In summary, this study shows that two KIR populations work collaboratively to govern electrical communication and the spread of vasomotor responses along cerebral arteries.

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