Modulation of Ca by agents affecting voltage-sensitive Ca channels in mesangial cells

1989 ◽  
Vol 257 (6) ◽  
pp. F1094-F1099 ◽  
Author(s):  
Y. M. Yu ◽  
F. Lermioglu ◽  
A. Hassid

The purpose of this study was to investigate the effects of depolarizing media and of Ca-channel activators and blockers on cytosolic free Ca in cultured rat mesangial cells. Membrane depolarizing media, containing 10–100 mM K+, dose dependently increased cytosolic Ca, and this effect was sustained and reversible. Nifedipine and lanthanum ion inhibited this increase, whereas verapamil was ineffective. A Ca-channel activator, BAY K 8644, dose dependently increased resting Ca levels, and nifedipine inhibited this effect. Moreover, the increase of Ca induced by maximally effective high K+ and BAY K 8644 was additive, suggesting differential mechanisms of action for the two channel activators. Nifedipine and verapamil decreased resting Ca levels by up to 35–40%. The results support the idea that mesangial cells have spontaneously active Ca channels that can be further activated by membrane depolarization or by the Ca-channel activator, BAY K 8644, and inhibited by the Ca-channel blockers, nifedipine or verapamil. Voltage-sensitive Ca channels in mesangial cells may play a role in the regulation of the glomerular filtration rate.

2006 ◽  
Vol 96 (1) ◽  
pp. 218-234 ◽  
Author(s):  
Andrei I. Ivanov ◽  
Ronald L. Calabrese

In leeches, two pairs of reciprocally inhibitory heart interneurons that form the core oscillators of the pattern-generating network for heartbeat possess both high- and low-threshold (HVA and LVA) Ca channels. LVA Ca current has two kinetically distinct components (one rapidly activating/inactivating, ICaF, and another slowly activating/inactivating, ICaS) that mediate graded transmission, generate plateau potentials driving burst formation, and modulate spike-mediated transmission between heart interneurons. Here we used different stimulating protocols and inorganic Ca channel blockers to separate the effects of ICaF and ICaS on graded synaptic transmission and determine their interaction and relative efficacy. Ca2+ entering by ICaF channels is more efficacious in mediating release than that entering by ICaS channels. The rate of Ca2+ entry by LVA Ca channels appears to be as critical as the amount of delivered Ca2+ for synaptic transmission. LVA Ca currents and associated graded transmission were selectively blocked by 1 mM Ni2+, leaving spike-mediated transmission unaffected. Nevertheless, 1 mM Ni2+ affected homosynaptic enhancement of spike-mediated transmission that depends on background Ca2+ provided by LVA Ca channels. Ca2+ provided by both ICaF and ICaS depletes a common pool of readily releasable synaptic vesicles. The balance between availability of vesicles and Ca2+ concentration and its time course determine the strength of inhibitory transmission between heart interneurons. We argue that Ca2+ from multichannel domains arising from ICaF channels, clustered near but not directly associated with the release trigger, and Ca2+ radially diffusing from generally distributed ICaS channels interact at common release sites to mediate graded transmission.


1996 ◽  
Vol 107 (5) ◽  
pp. 621-630 ◽  
Author(s):  
M F Wilkinson ◽  
S Barnes

High-voltage activated Ca channels in tiger salamander cone photoreceptors were studied with nystatin-permeabilized patch recordings in 3 mM Ca2+ and 10 mM Ba2+. The majority of Ca channel current was dihydropyridine sensitive, suggesting a preponderance of L-type Ca channels. However, voltage-dependent, incomplete block (maximum 60%) by nifedipine (0.1-100 microM) was evident in recordings of cones in tissue slice. In isolated cones, where the block was more potent, nifedipine (0.1-10 microM) or nisoldipine (0.5-5 microM) still failed to eliminate completely the Ca channel current. Nisoldipine was equally effective in blocking Ca channel current elicited in the presence of 10 mM Ba2+ (76% block) or 3 mM Ca2+ (88% block). 15% of the Ba2+ current was reversibly blocked by omega-conotoxin GVIA (1 microM). After enhancement with 1 microM Bay K 8644, omega-conotoxin GVIA blocked a greater proportion (22%) of Ba2+ current than in control. After achieving partial block of the Ba2+ current with nifedipine, concomitant application of omega-conotoxin GVIA produced no further block. The P-type Ca channel blocker, omega-agatoxin IVA (200 nM), had variable and insignificant effects. The current persisting in the presence of these blockers could be eliminated with Cd2+ (100 microM). These results indicate that photoreceptors express an L-type Ca channel having a distinguishing pharmacological profile similar to the alpha 1D Ca channel subtype. The presence of additional Ca channel subtypes, resistant to the widely used L-, N-, and P-type Ca channel blockers, cannot, however, be ruled out.


1986 ◽  
Vol 251 (6) ◽  
pp. F1018-F1028
Author(s):  
A. Hassid ◽  
N. Pidikiti ◽  
D. Gamero

We have used the “second generation” Ca indicator, fura-2, to measure cytosolic free Ca concentrations in superfused cultures of adherent primary renal mesangial cells. The basal cytosolic free Ca concentration in these cells was found to be 93 +/- 5 nM (n = 35). The Ca ionophore ionomycin (0.1 microM) increased cytosolic Ca levels to a peak value of fourfold above basal, followed by a decline to a steadily maintained concentration of twofold above basal. Two vasoactive peptide hormones, arginine vasopressin and angiotensin II, at maximally effective concentrations, transiently increased cytosolic free Ca levels to peak values of three- and sixfold, respectively, above basal levels. The angiotensin II-evoked increase declined to near basal values before rising again to a value of 1.5- to 2-fold above basal. Cells treated with vasopressin did not have a significant secondary increase of Ca above a small, time-dependent, spontaneous increase. Mesangial cells demonstrated tachyphylaxis to both peptides. However, cross-tachyphylaxis was not observed. Treatment of cells with angiotensin II in ethyleneglycol-bis-(beta-aminoethylether)-N,N'-tetraacetic acid-supplemented Ca-deficient medium, or with the Ca channel blockers nifedipine or verapamil, did not eliminate the transient phase of cytosolic Ca metabolism. In contrast, the Ca channel blockers completely inhibited the second sustained Ca response to angiotensin II. These results indicate that angiotensin II and vasopressin mobilize intracellular Ca in cultured adherent mesangial cells. Angiotensin II, but not vasopressin, also appears to increase cytosolic Ca by influx of extracellular Ca through specific channels.


1990 ◽  
Vol 95 (1) ◽  
pp. 1-27 ◽  
Author(s):  
H H Valdivia ◽  
R Coronado

The agonist effect of the dihydropyridine (DHP) (-)Bay K 8644 and the inhibitory effects of nine antagonist DHPs were studied at a constant membrane potential of 0 mV in Ca channels of skeletal muscle transverse tubules incorporated into planar lipid bilayers. Four phenylalkylamines (verapamil, D600, D575, and D890) and d-cis-diltiazem were also tested. In Ca channels activated by 1 microM Bay K 8644, the antagonists nifedipine, nitrendipine, PN200-110, nimodipine, and pure enantiomer antagonists (+)nimodipine, (-)nimodipine, (+)Bay K 8644, inhibited activity in the concentration range of 10 nM to 10 microM. Effective doses (ED50) were 2 to 10 times higher when HDPs were added to the internal side than when added to the external side. This sidedness arises from different structure-activity relationships for DHPs on both sides of the Ca channel since the ranking potency of DHPs is PN200-110 greater than (-)nimodipine greater than nifedipine approximately S207-180 on the external side while PN200-110 greater than S207-180 greater than nifedipine approximately (-)nimodipine on the internal side. A comparison of ED50's for inhibition of single channels by DHPs added to the external side and ED50's for displacement of [3H]PN200-110 bound to the DHP receptor, revealed a good quantitative agreement. However, internal ED50's of channels were consistently higher than radioligand binding affinities by up to two orders of magnitude. Evidently, Ca channels of skeletal muscle are functionally coupled to two DHP receptor sites on opposite sides of the membrane.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Sayed Tariq ◽  
James Anderson ◽  
Rohit Dhingra ◽  
Mikhail Torosoff

Background: Effects of anti-hypertensive medications on left ventricular dimensions and systolic function in patients with arterio-venous (AV) fistulas have not been well investigated. Material and Methods: Medical charts and echocardiograms of 346 patients with AV fistula were reviewed. Of 346, 149 patients had TTE prior to the AV fistula surgery, 197 had TTE after the AV fistula surgery, and 76 patients had TTE before and after the AV fistula surgery. Data on medication use was available in 314 patients. ANOVA, chi-square, and logistic regression tests were employed. Results: In patients scheduled for AV fistula placement, 20% (31/149) patients had systolic dysfunction and 15% (22/142) had increased LV end-diastolic dimensions (LVEDD). Moderate systolic LV dysfunction was observed in 6% (9/149) and additional 8% (12/149) had severe LV dysfunction. Increased LVEDD with some LV dysfunction was noted in 27% (38/142).Following the AV fistula placement, 18% (36/197) of patients had systolic dysfunction and 12% (22/187) had increased LV end-diastolic dimensions (LVEDD). Moderate or severe systolic LV dysfunction was observed in 6% (5/197). LV systolic dysfunction or dilatation was noted in 23% (43/187). Of 314 patients, 63% were on beta-blockers (BB), 25% were on ACE inhibitor or an ARB , 43% on calcium-channel blocker , and 15% on alpha-antagonist . BB, ACEi-ARB, or AA were not associated with increased LVEDD or systolic dysfunction before or after the AV fistula placement. Prior to AV fistula, CCB treatment was not related to LV dilatation (36% in each group, p=0.981) Post AV fistula, CCB treatment was associated with increased LV dimensions (71% vs. 46%, p=0.029) but not LV systolic dysfunction (49% in LV dysfunction vs. 38% in the rest, p=0.446) . This association persisted after adjustment for co-morbidities and demographic parameters. Conclusions: LV systolic dysfunction and/or dilatation are common in patients undergoing AV fistula surgery. Despite decreased use of Ca-channel blockers in patients with LV dysfunction prior to AV fistula, Ca-channel blockers are associated with increased LV dimensions post AV fistula, and probably should be avoided in this vulnerable patient population.


Immunobiology ◽  
1994 ◽  
Vol 191 (1) ◽  
pp. 38-51 ◽  
Author(s):  
Nils P. Hailer ◽  
Roman A. Blaheta ◽  
Sebastian Harder ◽  
Martin Scholz ◽  
Albrecht Encke ◽  
...  

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