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At least 163 records · Page 9Linked to original sources
PubMed2002

The role of the sarcoplasmic reticulum in neonatal uterine smooth muscle: enhanced role compared to adult rat.

Little is known about contractile activity, response to agonists or excitation-contraction coupling in neonatal smooth muscle. We have therefore investigated 10-day rat uterus to better understand these processes, and compared it to adult uterus to elucidate how control of contractility develops. Spontaneous contractions are present in the 10-day neonatal uterus, although they are not as large or as regular as those present in adult tissues. External Ca(2+) entry via L-type Ca(2+) channels is the sole source of Ca(2+) and is essential for the spontaneous activity. The neonatal uterus was responsive to carbachol or prostaglandin F(2alpha) application; it showed a marked stimulation and a clear dissociation between the force and Ca(2+) changes. Such sensitization was not apparent in adult rat myometrium. The sarcoplasmic reticulum (SR) had more releasable Ca(2+) and contributed more to the response to agonists in neonatal compared to adult tissues. Thus, Ca(2+) entry as opposed to SR Ca(2+) release contributed much less to the uterine response to agonists in the neonatal, compared to adult tissues. Inhibition of the SR by cyclopiazonic acid also caused a more vigorous increase in Ca(2+) and contractile activity, particularly frequency, in the neonatal compared to the adult uterus. Taken together these data suggest that: (1) spontaneous activity is already present by day 10, (2) receptor-coupling and excitation-contraction signalling pathways are functional, (3) the SR and Ca(2+) sensitization mechanisms play a more prominent role in the neonate, and (4) there is a shift to a greater reliance on Ca(2+) entry and excitability with development of the myometrium.

Aging↗
PubMed2006

CCCP enhances catecholamine release from the perfused rat adrenal medulla.

The present study was designed to investigate the effect of carbonyl cyanide m-chlorophenylhydrazone (CCCP), a mitochondrial uncoupler, on secretion of catecholamines from the isolated perfused model of the rat adrenal gland and to establish the mechanism of its adrenomedullary secretion. The perfusion of CCCP (3x10(-5) M) into an adrenal vein of for 90 min caused a great increase in catecholamine secretion. Tachyphylaxis to catecholamine-releasing effect of CCCP was not observed by repeated perfusion of it. The net catecholamine-releasing effects of CCCP were depressed by pretreament with pirenzepine (a selective muscarinic M(1)-receptor antagonist), chlorisondamine (a selective neuronal nicotinic receptor antagonist), nicardipine (an L-type Ca2+-channel antagonist), TMB-8 (an intracellular Ca2+-antagonist), and the perfusion of EGTA plus Ca2+-free medium, respectively. In the presence of CCCP (3x10(-5) M), catecholamine secretory responses induced by ACh (5.32x10(-3) M), high K+ (5.6x10(-2) M, a direct membrane depolarizer), DMPP (10(-4) M, (a selective neuronal nicotinic receptor agonist), and McN-A-343 (10(-4) M, (a selective muscarinic M1-receptor agonist) were significantly enhanced. CCCP also significantly enhanced the catecholamine secretory responses evoked by Bay-K-8644 (10(-5) M), L-type Ca2+ channel activator, and cyclopiazonic acid (10(-5) M), an inhibitor of Ca2+-ATPase. Furthermore, the perfusion of FCCP (3x10(-5) M), a similar mitochondrial uncoupler, into an adrenal vein of for 90 min also caused a great increase in catecholamine secretion in a similar pattern with CCCP. Taken together, the results demonstrate that CCCP causes the catecholamine secretion from the perfused rat adrenal medulla in a calcium-dependent fashion. It is thought that this catecholamine secretory enhancement of CCCP may be mediated by both cholinergic receptor stimulation and membrane depolarization, which are relevant to the cytoplasmic Ca2+ increase by stimulation of the Ca2+ influx as well as by the inhibition of Ca2+ uptake into the cytoplasmic Ca2+ stores (both endoplasmic reticulum and mitochondria in chromaffin cells). It also seems that protonophores, such as CCCP, suppress mitochondrial Ca2+ uptake and increase the stimulated secretion of catecholamine by the secretagogues. These results indicate that mitochondria modulate catecholamine secretion by regulating the Ca2+ mobilization for exocytosis.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Endothelin-1 contracts isolated vessels independently of dihydropyridine-sensitive Ca2+ channel activation.

Spirally cut strips of arteries and veins were prepared from the rabbit or the dog and superfused in cascade. Venous strips were more sensitive to endothelin-1 (ET-1) than arterial ones and, in particular, the rabbit jugular and the rabbit mesenteric veins were contracted by as little as 0.5-2.5 pmol of ET-1 in a reproducible and dose-dependent way. The calcium agonist Bay K 8644 had a different profile of activity on the vascular strips, being more potent on the rabbit mesenteric artery than on the rabbit jugular or mesenteric veins. Nicardipine (10(-7) M) did not affect the ET-1-induced vascular contractions but abolished the contractile activity of Bay K 8644. Contractions induced by ET-1 were not affected by the kininase II inhibitor captopril in the rabbit jugular veins but were potentiated by methylene blue in both veins of the rabbit. Our results indicate that ET-1 potently contracts venous and arterial isolated vessels via the activation of specific receptors or channels that differ from the dihydropyridine-sensitive calcium channels. The fact that ET-1 is more active on venous than on arterial smooth muscle may have important pathophysiological implications.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Ca-agonists: a new class of inotropic drugs.

The basic pharmacology of dihydropyridine Ca-agonists published so far (BAY k8644, CGP 28-392, H 160/51, YC 170, and 202-791) is described. The importance of the potency of the enantiomeres for the effect of a racemic compound is underlined. The Ca agonist prototype BAY k8644 leads to an increase of the maximal rate of rise of left ventricular pressure (LV(dP/dt)) and an increase of left ventricular stroke work in conscious dogs. When the vascular effects of BAY k8644 are counterbalanced by intravenous injection of sodium-nitroprusside, the left ventricular functions curves show markedly increased stroke work against the same mean arterial blood pressure at the same filling pressure. BAY k8644 stimulates the heart economically: the net efficiency in isolated working guinea-pig hearts is about 20%, identical to a stimulation by calcium or ouabain. Cardiotonic drugs acting via cAMP-dependent mechanisms like isoprenaline, amrinone, or pimobendane however, stimulate the heart about 1/3 less economically. The mechanism of action of Ca-agonists is explained from electrophysiological findings: Ca-agonistic dihydropyridines increase the open probability of the Ca-channels by a shift of the open-probability curve to more negative membrane potentials. As a consequence, the steady-state inactivation curve of the Ca-channel is also shifted in the same direction. While the effect on open-probability is the underlying mechanism for Ca-agonism, the latter effect results in Ca-antagonism. Therefore, depending on drug concentration and on membrane resting potential, a single chemical compound can act either as a Ca-agonist or a Ca-antagonist. A kinetic model of dihydropyridine action on the Ca-channel is described.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1994

Blockers of Ca2+ channels in the plasmalemma of perfused Characeae cells.

Ionic currents in the plasmalemma of perfused Nitella syncarpa cells identified as currents through Ca2+ channels were registered for the first time. The effect of 1,4-dihydropyridine derivatives (nifedipine, nitrendipine, riodipine) and phenylalkylamines (verapamil, D600) as well as the agonist CGP-28392 on the Ca2+ channels in the plasmalemma of perfused cells of Nitellopsis obtusa and Nitella syncarpa have been studied. A blocking effect of 1,4-dihydropyridine derivatives and phenylalkylamines on the plasmalemma Ca2+ channels has been detected. Phenylalkylamines have been found to block both inward and outward Ca2+ currents. The activating effect of the agonist CGP-28392 on the Ca2+ channels of plasmalemma has been shown.

Calcium Channel Agonists↗
PubMed1994

Trichokonin VI, a new Ca2+ channel agonist in bullfrog cardiac myocytes.

The effects of trichokonin VI (= gliodeliquescin A), a peptaibol isolated from the culture broth of Trichoderma koningii Oudemans, on L-type Ca2+ channel currents in single bullfrog atrial cells were investigated. Our results showed that trichokonin VI is a new potent agonist of L-type Ca2+ channels in cardiac membranes.

Alamethicin↗
PubMed1996

Thyrotropin (TSH)-releasing hormone stimulates TSH beta promoter activity by two distinct mechanisms involving calcium influx through L type Ca2+ channels and protein kinase C.

TRH stimulates rat (r) TSH beta gene promoter activity at two distinct response elements, which also respond to protein kinase C-signaling pathways. The dependence of TRH-stimulated transcription of the TSH beta gene on a rise in intracellular calcium [Ca2+]i, and on the necessity for Ca2+ influx through L-type voltage-gated calcium channels was investigated in two transfected cell lines and in normal thyrotropes. The transcription rate of the homologous gene in normal thyrotropes was measured by nuclear run-off assays. Bay K8644, an L channel agonist, stimulated TSH beta gene transcription 6-fold, and TRH stimulation of TSH beta gene transcription was partially blocked by nimodipine, an L channel antagonist, while phorbol 12-myristate-13-acetate (PMA)-stimulated transcription was not. Bay K8644 plus TRH had a greater effect than either treatment alone. Constructs of the 5'-flanking region of the TSH beta gene fused to the luciferase reporter (TSH beta LUC) were then transfected into excitable GH3 pituitary cells. TSH beta LUC was stimulated 2- to 5-fold by 1 nM TRH or 100 nM Bay K8644, and the TRH effect was nearly abolished by nimodipine or chelation of external Ca2+. Constructs containing isolated TRH-responsive elements fused to a heterologous promoter responded similarly. The protein kinase C activator, PMA (100 nM) also stimulated TSH beta LUC transcription, but its effect was not inhibited by nimodipine. A stable heterologous cell line containing the mouse TRH receptor was constructed by transfection of nonexcitable 293 cells, which lack L channel activity. In the resultant 301 cells, TSH beta LUC activity was increased 2- to 3-fold by TRH or PMA; nimodipine, Bay K8644, and removal of extracellular Ca2+ had no effect. We conclude that TRH stimulation of TSH beta gene transcription requires Ca2+ release from inositol triphosphate-sensitive stores and Ca2+ influx via L-type calcium channels in GH3 cells, but in transfected 293 cells TRH activation of protein kinase C plays a predominant role in activating TSH beta. Both mechanisms appear to be operative in normal thyrotropes.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2005

G-protein-coupled receptor modulation of striatal CaV1.3 L-type Ca2+ channels is dependent on a Shank-binding domain.

Voltage-gated L-type Ca2+ channels are key determinants of synaptic integration and plasticity, dendritic electrogenesis, and activity-dependent gene expression in neurons. Fulfilling these functions requires appropriate channel gating, perisynaptic targeting, and linkage to intracellular signaling cascades controlled by G-protein-coupled receptors (GPCRs). Surprisingly, little is known about how these requirements are met in neurons. The studies described here shed new light on how this is accomplished. We show that D2 dopaminergic and M1 muscarinic receptors selectively modulate a biophysically distinctive subtype of L-type Ca2+ channels (CaV1.3) in striatal medium spiny neurons. The splice variant of these channels expressed in medium spiny neurons contains cytoplasmic Src homology 3 and PDZ (postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1) domains that bind the synaptic scaffolding protein Shank. Medium spiny neurons coexpressed CaV1.3-interacting Shank isoforms that colocalized with PSD-95 and CaV1.3a channels in puncta resembling spines on which glutamatergic corticostriatal synapses are formed. The modulation of CaV1.3 channels by D2 and M1 receptors was disrupted by intracellular dialysis of a peptide designed to compete for the CaV1.3 PDZ domain but not with one targeting a related PDZ domain. The modulation also was disrupted by application of peptides targeting the Shank interaction with Homer. Upstate transitions in medium spiny neurons driven by activation of glutamatergic receptors were suppressed by genetic deletion of CaV1.3 channels or by activation of D2 dopaminergic receptors. Together, these results suggest that Shank promotes the assembly of a signaling complex at corticostriatal synapses that enables key GPCRs to regulate L-type Ca2+ channels and the integration of glutamatergic synaptic events.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Involvement of dihydropyridine-sensitive calcium channels in human dendritic cell function. Competition by HIV-1 Tat.

The entry of extracellular calcium in leukocytes mediates several cellular processes; however, unlike in excitable tissues, the underlying molecular mechanisms are poorly defined. In this paper we provide phenotypical and biochemical evidence that peripheral blood-derived human dendritic cells express dihydropyridine-sensitive calcium channels. Exposure to the dihydropyridine drug nifedipine, which binds L-type calcium channels blocking calcium influx, prevents two dendritic cell functions that are dependent on extracellular calcium entry: apoptotic body engulfment and interleukin-12 production induced by cross-linking of the surface lectin NKRP1A. It is known that exogenous human immunodeficiency virus, type 1 Tat affects several Ca2+-dependent immune cell responses. Here we demonstrate that Tat inhibits apoptotic body engulfment and interleukin-12 production by blocking extracellular calcium influx. This inhibition is prevented by the calcium channel agonist dihydropyridine derivative Bay K 8644, suggesting the involvement of L-type calcium channels. This hypothesis is further supported by the observation that Tat and dihydropyridine drugs compete for binding to dendritic cells. Taken together, these findings indicate that exogenous Tat exerts its inhibitory effects on dendritic cells by blocking dihydropyridine-sensitive L-type calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

[Function and pharmacology of potassium channels in heart and vessels].

The variability of the potassium channels in the cardiac tissues is remarkable. There are two main classes: voltage-operated channels and ligand-operated channels. The voltage-operated channels play a dominant role in the genesis of the resting potential (iK1) and the different phases of the action potential, the transient current ito during the initial phase of repolarisation, the iKp current and the slow current iK during the plateau phase. This class also includes the acetylcholine activated channel, iK(Ach). The ligand-operated channels seem to play a role in pathological situations such as ischaemia and anoxia: these channels are activated by a reduction in intracellular ATP or an increase in intracellular fatty acids or Na+. Substances blocking the iK and ito potassium channels have an anti-ischaemic effect. The agonists of ATP channels have a great therapeutic potential in vascular pathology, especially in the treatment of hypertension.

Action Potentials↗
PubMed2006

Effects of testosterone on hormonal content and calcium-dependent basal secretion in female rat pituitary cells.

In vivo and in vitro effects of elevated androgens on agonist-induced gonadotropin secretion have been addressed previously. Here we investigated the effects of testosterone on hormonal content and basal (in the absence of agonists) hormone release in pituitary lactotrophs, somatotrophs and gonadotrophs from female rats. Furthermore we tested the hypothesis that testosterone action is dependent on the pattern of spontaneous and Bay K 8644 (a L-type calcium channel agonist) -induced calcium signalling. Mixed anterior pituitary cells were cultured in steroid containing or depleted media, and testosterone (1pM to 10nM) was added for 48h. Cells were studied for their spontaneous and Bay K 8644-induced calcium signalling pattern and total hormone levels (release and hormonal content). In lactotrophs, somatotrophs and gonadotrophs testosterone did not affect the pattern of spontaneous calcium signalling. Bay K 8644-induced calcium signalling and hormone release were not affected by testosterone. In both steroid-depleted and -containing medium, testosterone inhibited prolactin (PRL), luteinizing hormone (LH) and growth hormone (GH) cellular content and release in a dose-dependent manner, with IC(50)s in a sub-nanomolar concentration range. These results indicate that testosterone inhibits basal hormone release from lactotrophs, somatotrophs and gonadotrophs without affecting intracellular calcium signalling. This action of testosterone is not dependent on the presence of other steroid hormones.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

[Interaction of calcium agonists and antagonists with Ca-binding proteins and their effect on cyclic nucleotide phosphodiesterase].

The effects of Ca2+ antagonists (nicardipine, felodipine, nitrenedipine, isradipine, niphedipine, darodipine and riodipine) and Ca2+ agonists (BAY K8644 and CGP 28392), 1.4-dihydropyridine derivatives (1.2-DHP), on the calmodulin (CM)-dependent activation of cyclic nuxleotide phosphodiesterase (PDE) were studied. Both the blockers and activators of slow potential-dependent Ca2+ channels induced a un-competitive inhibition of the CM-dependent PDE activity. 1.4-DHP was found to replace the fluorescent probe, diS-C3-(5), from the Ca2(+)-dependent calmodulin-dye complex (K0.5 = 4-60 microM) but at concentrations below 100 microM had no effect on the Ca2(+)-dependent troponin C-dye complex. Darodipine (100 microM) did not interact with the proteins. The 1.4-DHP interaction with CM did not interfere with PDE activation. It is concluded that 1.4-DHP may affect Ca2+ dependent processes not only at the levels of activation or blocking of Ca2+ channels, but also through regulation of Ca2(+)-CM dependent enzymes.

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed2005

A role for L-type calcium channels in the maturation of parvalbumin-containing hippocampal interneurons.

While inhibitory interneurons are well recognized to play critical roles in the brain, relatively little is know about the molecular events that regulate their growth and differentiation. Calcium ions are thought to be important in neuronal development and L-type voltage gated Ca(+2) channels have been implicated in activity-dependent mechanisms of early-life. However, few studies have examined the role of these channels in the maturation of interneurons. The studies reported here were conducted in hippocampal slice cultures and indicate that the L-type Ca(+2) channel agonists and antagonists accelerate and suppress respectively the growth of parvalbumin-containing interneurons. The effects of channel blockade were reversible suggesting they are not the result of interneuronal cell death. Results from immunoblotting showed that these drugs have similar effects on the expression of the GABA synthetic enzymes, glutamic acid decarboxylase65, glutamic acid decarboxylase67 and the vesicular GABA transporter. This suggests that L-type Ca(+2) channels regulate not only parvalbumin expression but also interneuron development. These effects are likely mediated by actions on the interneurons themselves since the alpha subunits of L-type channels, voltage-gated calcium channel subunit 1.2 and voltage-gated calcium channel subunit 1.3 were found to be highly expressed in neonatal mouse hippocampus and co-localized with parvalbumin in interneurons. Results also showed that while these interneurons can contain either subunit, voltage-gated calcium channel subunit 1.3 was more widely expressed. Taken together results suggest that an important subset of developing interneurons expresses L-type Ca(+2) channels alpha subunits, voltage-gated calcium channel subunit 1.2 and especially voltage-gated calcium channel subunit 1.3 and that these channels likely regulate the development of these interneurons in an activity-dependent manner.

Animals↗
PubMed2001

Parathyroid cells express dihydropyridine-sensitive cation currents and L-type calcium channel subunits.

Parathyroid cells express Ca2+ -conducting currents that are activated by raising the extracellular Ca2+ concentration ([Ca2+]o). We investigated the sensitivity of these currents to dihydropyridines, the expression of voltage-dependent Ca(2+) channel (VDCC) subunits, and the effects of dihydropyridines on the intracellular free [Ca2+] ([Ca2+]i) and secretion in these cells. Dihydropyridine channel antagonists dose dependently suppressed Ca2+ -conducting currents, and agonists partially reversed the inhibitory effects of the antagonists in these cells. From a bovine parathyroid cDNA library, we isolated cDNA fragments encoding parts of an alpha(1S)- and a beta(3)-subunit of L-type Ca(2+) channels. The alpha(1S)-subunit cDNA from the parathyroid represents an alternatively spliced variant lacking exon 29 of the corresponding gene. Northern blot analysis and immunocytochemistry confirmed the presence of transcripts and proteins for alpha(1)- and beta(3)-subunits in the parathyroid gland. The addition of dihydropyridines had no significant effects on high [Ca2+]o-induced changes in [Ca2+]i and parathyroid hormone (PTH) release. Thus our studies indicate that parathyroid cells express alternatively spliced L-type Ca2+ channel subunits, which do not modulate acute intracellular Ca2+ responses or changes in PTH release.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1998

Potassium depolarization of mammalian vestibular sensory cells increases [Ca2+]i through voltage-sensitive calcium channels.

The existence of voltage-sensitive Ca2+ channels in type I vestibular hair cells of mammals has not been conclusively proven. Furthermore, Ca2+ channels present in type II vestibular hair cells of mammals have not been pharmacologically identified. Fura-2 fluorescence was used to estimate, in both cell types, intracellular Ca2+ concentration ([Ca2+]i) variations induced by K+ depolarization and modified by specific Ca2+ channel agonists and antagonists. At rest, [Ca2+]i was 90 +/- 20 nM in both cell types. Microperifusion of high-K+ solution (50 mM) for 1 s increased [Ca2+]i to 290 +/- 50 nM in type I (n = 20) and to 440 +/- 50 nM in type II cells (n = 10). In Ca2+-free medium, K+ did not alter [Ca2+]i. The specific L-type Ca2+ channel agonist, Bay K, and antagonist, nitrendipine, modified in a dose-dependent manner the K+-induced [Ca2+]i increase in both cell types with maximum effect at 2 microM and 400 nM, respectively. Ni2+, a T-type Ca2+ channel blocker, reduced K+-evoked Ca2+ responses in a dose-dependent manner. For elevated Ni2+ concentrations, the response was differently affected by Ni2+ alone, or combined to nitrendipine (500 nM). In optimal conditions, nitrendipine and Ni2+ strongly depressed by 95% the [Ca2+]i increases. By contrast, neither omega-agatoxin IVA (1 microM), a specific P- and Q-type blocker, nor omega-conotoxin GVIA (1 microM), a specific N-type blocker, affected K+-evoked Ca2+i responses. These results provide the first direct evidence that L- and probably T-type channels control the K+-induced Ca2+ influx in both types of sensory cells.

Animals↗
PubMed1989

Long-term inhibition of angiotensin converting enzyme suppresses calcium channel agonist-induced contraction of aorta in hypertensive rats.

To elucidate functional changes in the vascular smooth muscle of spontaneously hypertensive rats (SHR) after chronic inhibition of angiotensin converting enzyme, we examined the contractile responses to different pharmacological interventions in the isolated aortas from SHR treated with a novel angiotensin converting enzyme inhibitor, CS-622 (10 mg/kg/day) for 20 weeks. In normal K+ medium, a marked contraction was elicited by increasing Ca2+ concentration from 0 to 3 mM in aortas from a control group of SHR, but not in aortas from SHR treated with CS-622. In 60 mM K+ medium, however, the sensitivity of aorta to Ca2+ was almost the same in the two groups. A calcium channel activator, CGP-28392 (10(-7) to 10(-6) M), induced a marked contraction in the aortas from control SHR, but not in the aortas from CS-622-treated SHR. When slightly depolarized in 10 or 12 mM K+ solution, the aortas from CS-622-treated SHR contracted in response to CGP-28392. The aortic sensitivity to KCl contraction was much lower in CS-622-treated SHR than in untreated SHR, whereas the sensitivity to phenylephrine contraction was little different in the two groups. These contractile profiles of aortas from CS-622-treated SHR were very similar to those from normotensive Wistar-Kyoto rats but not to those from hydralazine-treated SHR. These data suggest that contractions due to Ca2+ through voltage-dependent calcium channels are exaggerated in SHR aorta and that long-term treatment with angiotensin converting enzyme inhibitor suppresses the abnormal contractility of SHR vascular smooth muscle, probably through alterations of voltage-related functions of calcium channels.

Animals↗
PubMed2004

Gap junctional communication modulates agonist-induced calcium oscillations in transfected HeLa cells.

Gap junctional communication modulates intercellular calcium signaling in many cell types. We have investigated whether gap junctional communication modulates calcium oscillatory behavior of cells responding to an agonist. Extracellular UTP induced calcium oscillations in 70% of HeLa cells cultured in monolayer, and neighboring cells oscillated independently of each other. In HeLa cell transfectants expressing connexin43 (HeLa/Cx43), extracellular UTP induced calcium transients, but calcium oscillations occurred in only 10% of cells. Inhibition of gap junctional communication with anandamide in HeLa/Cx43 transfectants substantially restored oscillations (55% of cells). In HeLa/Cx45 transfectants, UTP initiated calcium oscillations similar to those seen in HeLa cells (63% of cells), but HeLa/Cx46 transfectants demonstrated calcium oscillations that were dampened compared to those of the parental HeLa cells, and occurred in only 40% of cells. These experiments demonstrate that gap junctional communication modulates calcium oscillatory behavior in cell monolayers, presumably by allowing cells to share a small molecule such as inositol trisphosphate. These studies suggest that gap junctional communication may alter the nature of signals induced by calcium mobilizing agonists in a connexin-dependent fashion by modulating calcium oscillatory behavior.

Animals↗