Calcium channel activation in vascular smooth muscle by BAY K 8644

1984 ◽  
Vol 62 (11) ◽  
pp. 1401-1410 ◽  
Author(s):  
C. M. Su ◽  
V. C. Swamy ◽  
D. J. Triggle
Keyword(s):  
Smooth Muscle ◽  
Dose Response ◽  
Response Curve ◽  
Bay K 8644 ◽  
Rat Tail Artery ◽  
Channel Activation ◽  
Tail Artery ◽  
Voltage Dependent ◽  
Adrenoceptor Agonists ◽  
Rat Tail

BAY K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate) and CGP 28 392 (ethyl-4(2-difluoromethoxyphenyl)-1,4,5,7-tetrahydro-2-methyl-5-oxofuro-[3,4-b]pyridine-3-carboxylate) are closely related in structure to nifedipine and other 1,4-dihydropyridine Ca2+ channel antagonists. However, both BAY K 8644 and CGP 28 392 serve as activators of Ca2+ channels. In the rat tail artery, responses to BAY K 8644 are dependent upon [Formula: see text] and prior stimulation by K+ or by the α-adrenoceptor agonists, phenylephrine and BHT 920 (6-allyl-2-amino-5,6,7,8,-tetrahydro-4H-thiazolo[4,5-d]azepin dihydrochloride). Responses are blocked noncompetitively by the Ca2+ channel antagonists D-600 ((−)-D-600 > (+)-D-600) and diltiazem, but competitively by nifedipine (pA2 = 8.27). This suggests that activator and inhibitor 1,4-dihydropyridines interact at the same site. BAY K 8644 potentiates K+ responses and Ca2+ responses in K+-depolarizing media. The leftward shift of the K+ dose–response curve produced by BAY K 8644 suggests that this ligand facilitates the voltage-dependent activation of the Ca2+ channel. The pA2 value for nifedipine antagonism of BAY K 8644 responses is significantly lower than that for nifedipine antagonism of Ca2+ responses in K+ (25–80 mM) depolarizing media (9.4–9.6), suggesting that the state of the channel may differ according to the activating stimulus.

Phenylephrine contracts rat tail artery by one electromechanical and three pharmacomechanical mechanisms

1995 ◽  
Vol 268 (1) ◽  
pp. H74-H81 ◽  
Author(s):  
X. L. Chen ◽  
C. M. Rembold
Keyword(s):  
Smooth Muscle ◽  
Isometric Force ◽  
Rat Tail Artery ◽  
Excitation Contraction Coupling ◽  
Contraction Coupling ◽  
Tail Artery ◽  
Low Concentrations ◽  
Voltage Dependent ◽  
High Concentrations ◽  
Rat Tail

There are at least four mechanisms hypothesized to account for excitation-contraction coupling in arterial smooth muscle. 1) Contractile agonists and changes in extracellular [K+] ([K+]o) induce contraction by depolarization, which increases Ca2+ influx; this is the only mechanism involving a change in membrane potential (Em). 2) Contractile agonists release Ca2+ from the intracellular Ca2+ store. 3) Contractile agonists increase Ca2+ influx without changing Em either by activating voltage-dependent L-type Ca2+ channels or by opening other Ca(2+)-permeable channels. 4) Contractile agonists increase intracellular Ca2+ ([Ca2+]i) sensitivity of force; this is the only mechanism that does not involve changes in [Ca2+]i. Each of these mechanisms has been demonstrated in intact, skinned, or dissociated smooth muscle preparations. However, these four mechanisms have not been compared in the same preparation. The goal of this study was to determine which of these four contractile mechanisms are physiologically relevant in the intact rat tail artery. We stimulated deendothelialized rat tail artery with phenylephrine and high [K+]o. We then measured Em with microelectrodes, [Ca2+]i with fura 2, and isometric force with a strain gauge transducer. We find that all four mechanisms contributed to phenylephrine-induced rat tail artery contraction. The majority of phenylephrine-induced contraction was caused by depolarization and by increases in the [Ca2+]i sensitivity of force. Low concentrations of phenylephrine also increased [Ca2+] independent of changes in Em, potentially by increases in Ca2+ influx. Release of Ca2+ from intracellular stores was only observed with high concentrations of phenylephrine. Smooth muscle appears to invoke multiple mechanisms for excitation-contraction coupling.

Desensitization of the vascular contractile response to cumulative doses of α2-adrenoceptor agonists

1986 ◽  
Vol 64 (10) ◽  
pp. 1343-1345 ◽  
Author(s):  
D. W. Cheung
Keyword(s):  
Dose Response ◽  
Saphenous Vein ◽  
Contractile Response ◽  
Rat Tail Artery ◽  
Contractile Responses ◽  
Tail Artery ◽  
Α2 Adrenoceptor ◽  
Adrenoceptor Agonists ◽  
Rat Tail

Contractile responses to single or cumulative doses of α-adrenoceptor agonists were compared in the tail artery and the saphenous vein of the rat. In the rat tail artery, there were no differences in the dose–response relationships to noradrenaline, methoxamine, and KCl whether the agonists were applied as single or cumulative doses. However, the responses to single doses of clonidine and B-HT 920 were significantly larger than similar doses applied cumulatively. In the rat saphenous vein, responses to single doses of noradrenaline, clonidine, and B-HT 920 were also significantly larger than the corresponding cumulative doses. However, there was no difference in the responses to KCl. It was suggested that desensitization of α2-adrenoceptors in these vessels may result in the diminished responses to cumulative doses of the agonists. Desensitization appeared to be specific to α2-adrenoceptors, since the effect was not observed in responses mediated by the α1-adrenoceptors and KCl.

Two types of calcium channels in isolated smooth muscle cells from rat tail artery

1989 ◽  
Vol 256 (5) ◽  
pp. H1361-H1368 ◽  
Author(s):  
R. Wang ◽  
E. Karpinski ◽  
P. K. Pang
Keyword(s):  
Smooth Muscle ◽  
Steady State ◽  
Calcium Channels ◽  
Rat Tail Artery ◽  
Inward Current ◽  
Tail Artery ◽  
Channel Current ◽  
Steady State Inactivation ◽  
Channel Currents ◽  
Rat Tail

Whole cell patch-clamp recordings were carried out on smooth muscle cells from rat tail artery in short-term culture to verify the existence of and to characterize the calcium channels that are present. Two types of voltage-dependent calcium channels were identified in 55 of 63 cells studied. The T-type calcium channel was activated at -50 mV, and the peak inward current occurred at -10 mV, whereas the L-type channel was activated at -20 mV, and the peak inward current occurred at +10 or +20 mV. The T-type channel current inactivated quickly in contrast to the much slower inactivation of the L-channel current. The voltage dependence of steady-state inactivation of the two channels was similar to that reported for other vascular smooth muscle preparations. An internal solution containing Cs2-aspartate maintained the calcium-channel currents for at least 20 min with only a 5-10% decline. BAY K 8644 had no effect on T-channel currents, but the L-channel current was increased by at least a factor of two. In addition, BAY K 8644 shifted the activation threshold, the peak inward current, and the steady-state inactivation-activation curves of L-type channel currents in the direction of hyperpolarization.

Nitric oxide relaxes rat tail artery smooth muscle by cyclic GMP-independent decrease in calcium sensitivity of myofilaments

Cell Calcium ◽  
2004 ◽  
Vol 36 (2) ◽  
pp. 165-173 ◽  
Author(s):  
A. Soloviev ◽  
V. Lehen’kyi ◽  
S. Zelensky ◽  
P. Hellstrand
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Cyclic Gmp ◽  
Calcium Sensitivity ◽  
Rat Tail Artery ◽  
Tail Artery ◽  
Rat Tail
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