Discrimination by nimodipine, but not by nifedipine, between phasic and tonic contractions of guinea-pig taenia coli induced by K+ depolarization

1995 ◽  
Vol 73 (11) ◽  
pp. 1600-1604 ◽  
Author(s):  
Sadaharu Usune ◽  
Takeshi Katsuragi ◽  
Tatsuo Furukawa

Effects of Ca2+ channel blockers, such as nifedipine, nimodipine, gallopamil, verapamil, diltiazem, loperamide, Mn2+ and Ni2+, and papaverine, on contractile responses to K+ depolarization were evaluated in longitudinal muscles of taenia coli isolated from guinea-pig. Depolarization with high K+ solution (K+, 40 mM) produced a biphasic (phasic and tonic) contraction, which was inhibited by the above blockers in a concentration-dependent manner. Ratios of IC50 for the phasic contraction to IC50 for the tonic contraction of nimodipine, verapamil, gallopamil, nifedipine, loperamide, diltiazem, papaverine, Ni2+, and Mn2+ were 516.1, 73.7, 22.0, 6.4, 5.3, 4.9, 1.2, 0.7, and 0.1, respectively, indicating that nimodipine suppressed the tonic contraction more effectively than the phasic contraction. In a fluorescence study with fura 2, K+ depolarization elicited an increase in intracellular free Ca2+, [Ca2+]i, which was coupled with the phasic and tonic contraction. The increases in [Ca2+]i coupled with both types of the contraction were abolished by exposure to Ca2+-free solution. In addition, the increase of [Ca2+]i coupled with the phasic contraction was abolished by nifedipine, 10−7 M, but not by nimodipine, 10−7 M, whereas the increase with the tonic contraction was suppressed by both nifedipine and nimodipine. These findings suggest that the phasic and tonic contractions evoked by K+ depolarization are due to increases in [Ca2+]i via activation of respective nimodipine-resistant and nimodipine-sensitive Ca2+ channels in the longitudinal muscles of the taenia coli. Accordingly, nimodipine, but not nifedipine, appears to be a useful tool for distinguishing between the phasic and tonic contractions.Key words: guinea-pig taenia coli, phasic contraction, tonic contraction, nimodipine, nifedipine, intracellular free Ca2+.

1964 ◽  
Vol 207 (4) ◽  
pp. 873-876 ◽  
Author(s):  
N. Urakawa ◽  
W. C. Holland

High-K medium produces a tonic contraction in guinea pig taenia coli. If muscle strips are preincubated in glucose-free medium, K produces only a phasic contraction. A comparison of Ca45 entry and tissue Ca changes in the two responses were made. Both responses are accompanied by an enhanced uptake of Ca45. In addition to an increased Ca45 uptake, a significant rise of tissue Ca was observed during the tonic contraction. No detectable changes in tissue Ca were noted in the phasic contraction. In light of modern theories of muscle contraction, it was proposed that in the phasic contraction, sufficient Ca is released from a cellular site to initiate contraction, whereas in the tonic contraction enough Ca crosses the membrane to initiate contraction. The transmembrane Ca transport involved in the latter response appeared to be dependent on metabolism.


1987 ◽  
Vol 45 (3) ◽  
pp. 317-325 ◽  
Author(s):  
Shinjiro NAKAJYO ◽  
Kiyomi MATSUOKA ◽  
Tomohiro KITAYAMA ◽  
Yutaka YAMAMURA ◽  
Kazumasa SHIMIZU ◽  
...  

1994 ◽  
Vol 266 (3) ◽  
pp. H1132-H1137
Author(s):  
G. Zhang ◽  
Y. Yamamoto ◽  
K. Miwa ◽  
H. Suzuki

In the guinea pig carotid artery with an intact endothelium, substance P (SP, 10(-10)-10(-7) M) relaxed the norepinephrine- (NE) contracted smooth muscles transiently, in a concentration-dependent manner. Acetylcholine (ACh, 10(-6) M) produced a sustained relaxation. SP and ACh also relaxed muscles contracted with high-K (29.6 mM) solution, with a similar form but with a reduced amplitude compared with findings in NE-contracted muscles. In the presence of nitroarginine (10(-5) M) and NE, the ACh-induced relaxation was transient, with a reduced amplitude, whereas the SP-induced relaxation was not significantly changed. In muscles contracted with high-K solution containing nitroarginine, neither SP nor ACh produced relaxation. SP (> 10(-11) M) transiently hyperpolarized the membrane, but only when this peptide was applied from the intimal side of the intact vessel, and the peak amplitude reached approximately 20 mV from the resting potential at 10(-8) M. ACh transiently hyperpolarized the membrane (the peak amplitude being approximately 10 mV), in both the adventitial and intimal applications. In high-K solution, neither SP nor ACh produced hyperpolarization. The amplitude of hyperpolarizations produced by SP did not significantly change in the presence of nitroarginine, oxyhemoglobin, or indomethacin. Thus, SP-induced relaxation seems to be produced mainly by endothelium-derived hyperpolarizing factor-induced hyperpolarization.


1985 ◽  
Vol 63 (8) ◽  
pp. 912-917 ◽  
Author(s):  
Arda-E-Viraf M. Minocherhomjee ◽  
Basil D. Roufogalis ◽  
John H. McNeill

The role of anions in the maintenance of tension in electrically driven left atria isolated from guinea pigs has been examined. The disulfonic stilbene anion-channel blockers SITS (4-acetamido-4′-isothiocyanostilbene 2′-disulfonate) and DIDS (4,4′-diisothiocyano-2,2′-stilbene disulfonate) decreased the contractile force developed in a time- and concentration-dependent manner. As in the red cell anion channel, DIDS was more potent than SITS, but the maximal inhibition of tension produced by N-(4-azido-2-nitrophenyl)-2-aminoethyl sulfonate (NAP-taurine) was considerably lower than the near maximal inhibition produced by SITS and DIDS. The inhibition by SITS and DIDS was irreversible, suggesting a covalent interaction, and could not be overcome by increasing the calcium concentration or the frequency of stimulation. Consistent with a requirement for chloride anion, substitution of chloride and bicarbonate by the impermeant anion gluconate did not support contraction, while only partial tension was maintained with the lipophilic anions acetate and thiocyanate. Incubation of atria with 400 μM SITS blocked both 36Cl and 45Ca uptake to a similar extent, whereas the efflux of both these ions was not affected by incubation of the atria with SITS. The blockade by disulfonic stilbene anion-channel blockers of the contraction of the guinea pig myocardium may result from impairment of excitation–contraction coupling.


1987 ◽  
Vol 45 (3) ◽  
pp. 317-325
Author(s):  
Shinjiro NAKAJYO ◽  
Kiyomi MATSUOKA ◽  
Tomohiro KITAYAMA ◽  
Yutaka YAMAMURA ◽  
Kazumasa SHIMIZU ◽  
...  

2015 ◽  
Vol 10 (2) ◽  
pp. 430 ◽  
Author(s):  
Sohaib Mushtaq ◽  
Mueen Ahmad Chaudhry ◽  
Hafiz Muhammad Abdul Rahman

<p><em>Abies pindrow</em> is widely used in traditional practice for the treatment of diarrhea and bronchitis and the present study was designed to validate its folkloric uses. The crude extract of <em>A. pindrow</em> inhibit spontaneously contracting (1-10 mg/mL) and high K<sup>+</sup> (80 mM)-induced pre-contracted rabbit jejun-um (3 mg/mL) in concentration dependent manner. A rightward shift in Ca<sup>+2</sup> concentration response curves was seen in the presence of crude extract (0.1-0.3), similar to verapamil. In isolated tracheal tissue, <em>A. pindrow</em> inhibited, high K<sup>+</sup> and carbachol (1 µM)-induced contractions, at 3 mg/mL and 10 mg/mL respectively, similar to that caused by verapamil. These results indicate the presence of calcium channels blocked activity in crude extract of <em>A. pindrow</em>, which provide sound basis for medicinal uses of<em> A. pindrow</em> in diarrhea and bronchitis.   </p><p> </p>


1996 ◽  
Vol 76 (5) ◽  
pp. 3059-3069 ◽  
Author(s):  
K. H. Holmes ◽  
N. B. Keele ◽  
V. L. Arvanov ◽  
P. Shinnick-Gallagher

1. Metabotropic glutamate receptor (mGluR)-agonist-induced hyperpolarizations and corresponding outward currents were analyzed in basolateral amygdala (BLA) neurons in rat brain slice preparations with current-clamp and single-electrode voltage-clamp recording to characterize the mGluR subtype(s) and the ion channel(s) mediating this response. 2. The mGluR agonist (1S,3R)-1-amino-cyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) induced a membrane hyperpolarization or outward current in BLA neurons in a concentration-dependent manner (median effective concentration = 34 microM; range = 10-200 microM); the 1S,3R-ACPD hyperpolarizations are recorded in 89% of neurons that accommodate or cease firing in response to a 400-ms depolarizing current injection (0.5 nA). 3. mGluR agonists elicited hyperpolarizations or outward currents in a concentration-dependent manner in the following rank order of potency: (2S,3S,4S)-alpha-(carboxycyclopropyl)glycine (L-CCG-I) > 1S,3R-ACPD > (s)-4-carboxyphenylglycine = (RS)-4-carboxy-3-hydroxyphenylglycine (4C3HPG) > L-aminophosphonobutyric acid > (1S,3S)-1-amino-cyclopentane-1,3-dicarboxylic acid. In contrast, the mGluR agonists quisqualate and ibotenate induced only depolarizations in the presence of D-2-amino-5-phosphonovalerate and 6-cyano-7-nitroquinoxaline-2,3-dione in BLA neurons. 4. The 1S,3R-ACPD-induced outward current is mediated through a large-conductance calcium-dependent potassium (BK) conductance. The BK channel blockers iberiotoxin and charybdotoxin blocked the response, as did the potassium channel blockers tetraethylammonium and 4-aminopyridine; the small-conductance calcium-activated potassium channel blocker apamin did not affect the response. 5. The mGluR-agonist-induced hyperpolarization is blocked in amygdala slices from animals pretreated with pertussis toxin (PTX). 1S,3R-ACPD hyperpolarizations were recorded in neurons contralateral but not ipsilateral to the site of PTX injection. 6. The antagonist (+/-)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) reduced significantly the 1S,3R-ACPD-induced hyperpolarization. 7. In conclusion, the relative potency of L-CCG-I and 4C3HPG in evoking only hyperpolarizations (outward currents) in accommodating neurons, and the observation that MCPG (500 microM) reduces the hyperpolarization, suggest that a group-II-like mGluR underlies the hyperpolarizing response. The mGluR-induced response is sensitive to iberiotoxin and to pretreatment with PTX, suggesting activation of BK channels through a group II mGluR linked to a PTX-sensitive G protein in BLA neurons.


1994 ◽  
Vol 71 (2) ◽  
pp. 561-574 ◽  
Author(s):  
E. P. Christian ◽  
J. Togo ◽  
K. E. Naper

1. Intracellular recordings were made from C-fiber neurons identified by antidromic conduction velocity in intact guinea pig nodose ganglia maintained in vitro, and whole-cell patch clamp recordings were made from dissociated guinea pig nodose neurons to investigate the contribution of various K+ conductances to action-potential repolarization. 2. The repolarizing phase of the intracellularly recorded action potential was prolonged in a concentration-dependent manner by charybdotoxin (Chtx; EC50 = 39 nM) or iberiatoxin (Ibtx; EC50 = 48 nM) in a subpopulation of 16/36 C-fiber neurons. In a subset of these experiments, removal of extracellular Ca2+ reversibly prolonged action-potential duration (APD) in the same 4/9 intracellularly recorded C-fiber neurons affected by Chtx (> or = 100 nM). These convergent results support that a Ca(2+)-activated K+ current (IC) contributes to action-potential repolarization in a restricted subpopulation of C-fiber neurons. 3. Tetraethylammonium (TEA; 1-10 mM) increased APD considerably further in the presence of 100-250 nM Chtx or Ibtx, or in nominally Ca(2+)-free superfusate in 14/14 intracellularly recorded C-fiber neurons. TEA affected APD similarly in subpopulations of neurons with and without IC, suggesting that a voltage-dependent K+ current (IK) contributes significantly to action-potential repolarization in most nodose C-fiber neurons. 4. Substitution of Mn2+ for Ca2+ reduced outward whole-cell currents elicited by voltage command steps positive to -30 mV (2-25 ms) in a subpopulation of 21/36 dissociated nodose neurons, supporting the heterogeneous expression of IC. The kinetics of outward tail current relaxations (tau s of 1.5-2 ms) measured at the return of 2-3 ms depolarizing steps to -40 mV were indistinguishable in neurons with and without IC, precluding a separation of the nodose IC and IK by a difference in deactivation rates. 5. Chtx (10-250 nM) reduced in a subpopulation of 3/8 C-fiber neurons the total outward current elicited by voltage steps depolarized to -30 mV in single microelectrode voltage-clamp recordings. TEA (5-10 mM) further reduced outward current in the presence of 100-250 nM Chtx in all eight experiments. The Chtx-sensitive current was taken to represent IC, and the TEA-sensitive current, the IK component contributing to action-potential repolarization. 6. Rapidly inactivating current (IA) was implicated in action-potential repolarization in a subpopulation of intracellularly recorded C-fiber neurons. In 4/7 neurons, incremented hyperpolarizing prepulses negative to -50 mV progressively shortened APD.(ABSTRACT TRUNCATED AT 400 WORDS)


1982 ◽  
Vol 32 (1) ◽  
pp. 149-157
Author(s):  
Fukiko UEDA ◽  
Tadashi KISHIMOTO ◽  
Hiroshi OZAKI ◽  
Norimoto URAKAWA
Keyword(s):  

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