Amazing T-type calcium channels: updating functional properties in health and disease

Nilius, Bernd; Carbone, Emilio

doi:10.1007/s00424-014-1481-7

Cited by 19 publications

(8 citation statements)

References 42 publications

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“…Additional studies will need to be performed to determine the exact role that HCN + /TTC + cells play in renal pacemaker tissues of the multi-calyceal urinary tract. HCN and TTC channels are important for various cellular processes including setting and stabilization of membrane potential (Mayer & Westbrook, 1983;Doan & Kunze, 1999;Meuth et al 2006;Nolan et al 2007), muscle tonicity (Kuo et al 2010;Abd El-Rahman et al 2013), cellular excitability (Day et al 2005;Li et al 2007;Sui et al 2007;Fenske et al 2013), cell proliferation (Taylor et al 2008;Oguri et al 2010;Gray et al 2013), and eliciting pacemaker excitation (Nilius & Carbone, 2014;Wahl-Schott et al 2014). Although our findings do not rule out any specific function for HCN + /TTC + cells of the minor calyx, physiological and anatomical studies of the upper urinary tract support a role for HCN + cells as renal pacemakers, akin to cardiac and murine renal pacemakers.…”

Section: Discussioncontrasting

confidence: 61%

Hyperpolarization‐activated cation and T‐type calcium ion channel expression in porcine and human renal pacemaker tissues

Hurtado

Smith

2016

Journal of Anatomy

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Renal pacemaker activity triggers peristaltic upper urinary tract contractions that propel waste from the kidney to the bladder, a process prone to congenital defects that are the leading cause of pediatric kidney failure. Recently, studies have discovered that hyperpolarization-activated cation (HCN) and T-type calcium (TTC) channel conductances underlie murine renal pacemaker activity, setting the origin and frequency and coordinating upper urinary tract peristalsis. Here, we determined whether this ion channel expression is conserved in the porcine and human urinary tracts, which share a distinct multicalyceal anatomy with multiple pacemaker sites. Double chromagenic immunohistochemistry revealed that HCN isoform 3 is highly expressed at the porcine minor calyces, the renal pacemaker tissues, whereas the kidney and urinary tract smooth muscle lacked this HCN expression. Immunofluorescent staining demonstrated that HCN(+) cells are integrated within the porcine calyx smooth muscle, and that they co-express TTC channel isoform Cav3.2. In humans, the anatomic structure of the minor calyx pacemaker was assayed via hematoxylin and eosin analyses, and enabled the visualization of the calyx smooth muscle surrounding adjacent papillae. Strikingly, immunofluorescence revealed that HCN3(+) /Cav3.2(+) cells are also localized to the human minor calyx smooth muscle. Collectively, these data have elucidated a conserved molecular signature of HCN and TTC channel expression in porcine and human calyx pacemaker tissues. These findings provide evidence for the mechanisms that can drive renal pacemaker activity in the multi-calyceal urinary tract, and potential causes of obstructive uropathies.

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Section: Discussioncontrasting

confidence: 61%

Hyperpolarization‐activated cation and T‐type calcium ion channel expression in porcine and human renal pacemaker tissues

Hurtado

Smith

2016

Journal of Anatomy

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“…The differences found in T-type calcium channels subtypes expression in TCs might suggest that T-type Ca 2+ channels may be involved in the initiation of action potentials in myometrium at TCs level and then continued at SMCs level. Taking into account that in the last 10 years, a plethora of functions was revealed for the T-type Ca 2+ channels, especially in the regulation of critical body functions, and that these channels are able to interact with other ion channels, membrane proteins or bioactive lipids (Nilius and Carbone 2014 ), we can hypothesize that the differences in expression might be under the pregnancy special hormonal environment. Therefore, steroid hormones and also oxytocin might influence T-type Ca 2+ channels higher expression (and not only) in TCs derived from pregnant myometrium, since it is known that TCs have steroid hormone receptors.…”

Section: Discussionmentioning

confidence: 99%

Isolated human uterine telocytes: immunocytochemistry and electrophysiology of T-type calcium channels

Creţoiu

Radu

Banciu

et al. 2014

Histochem Cell Biol

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Recently, telocytes (TCs) were described as a new cell type in the interstitial space of many organs, including myometrium. TCs are cells with very long, distinctive extensions named telopodes (Tps). It is suggested that TCs play a major role in intercellular signaling, as well as in morphogenesis, especially in morphogenetic bioelectrical signaling. However, TC plasma membrane is yet unexplored regarding the presence and activity of ion channels and pumps. Here, we used a combination of in vitro immunofluorescence and patch-clamp technique to characterize T-type calcium channels in TCs. Myometrial TCs were identified in cell culture (non-pregnant and pregnant myometrium) as cells having very long Tps and which were positive for CD34 and platelet-derived growth factor receptor-α. Immunofluorescence analysis of the subfamily of T-type (transient) calcium channels CaV3.1 and CaV3.2 presence revealed the expression of these ion channels on the cell body and Tps of non-pregnant and pregnant myometrium TCs. The expression in TCs from the non-pregnant myometrium is less intense, being confined to the cell body for CaV3.2, while CaV3.1 was expressed both on the cell body and in Tps. Moreover, the presence of T-type calcium channels in TCs from non-pregnant myometrium is also confirmed by applying brief ramp depolarization protocols. In conclusion, our results show that T-type calcium channels are present in TCs from human myometrium and could participate in the generation of endogenous bioelectric signals responsible for the regulation of the surrounding cell behavior, during pregnancy and labor.

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“…The T-type calcium channel is a low-voltage calcium channel that has become a potential target for treating many diseases [14]. Nevertheless, little is known about the function of T-type calcium channels in human parturition and preterm labor.…”

Section: Discussionmentioning

confidence: 99%

TRPC3 Overexpression Promotes the Progression of Inflammation-Induced Preterm Labor and Inhibits T Cell Activation

Chen¹,

Dongming²,

Chen³

et al. 2018

Cell Physiol Biochem

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Background/Aims: To detect the expression of the TRPC3 channel protein in the tissues of women experiencing preterm labor and investigate its interaction with T lymphocytes, providing a theoretical basis for the clinical prevention of threatened preterm labor and the development of drug-targeted therapy. Methods: Forty-seven women experiencing preterm labor and 47 women experiencing normal full-term labor were included in this study. All included women underwent delivery via cesarean section; uterine samples were obtained at delivery. The expression of TRPC3 in uterine tissue was detected by immunohistochemistry, real-time quantitative reverse transcription-PCR, and western blot assay. Activation of T lymphocytes in peripheral blood and uterine tissue were detected by flow cytometry. A TRPC3^-/- mouse model of inflammation-induced preterm labor was established; expression of TRPC3, Cav3.1, and Cav3.2 were analyzed in mouse uterine tissue. Activation of T lymphocytes in female mouse and human peripheral blood samples was determined using flow cytometry. Results: In women experiencing preterm labor, expression of TRPC3 and the Cav3.1 and Cav3.2 proteins was significantly increased; in addition, the percentage of CD3⁺, CD4⁺, and CD8⁺ T cells in peripheral blood was significantly decreased. TRPC3 knockout significantly delayed the occurrence of preterm labor in mice. The muscle tension of ex vivo uterine strips was lower, Cav3.1 and Cav3.2 protein expression was lower, and the percentage of CD8⁺ T lymphocytes was significantly increased in wild-type mice subjected to an inflammation-induced preterm labor than in wild-type mice experiencing normal full-term labor. Conclusion: TRPC3 is closely related to the initiation of labor. TRPC3 relies on Cav3.1 and Cav3.2 proteins to inhibit inflammation-induced preterm labor by inhibiting the activation of T cells, in particular CD8⁺ T lymphocytes.

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Amazing T-type calcium channels: updating functional properties in health and disease

Cited by 19 publications

References 42 publications

Hyperpolarization‐activated cation and T‐type calcium ion channel expression in porcine and human renal pacemaker tissues

Hyperpolarization‐activated cation and T‐type calcium ion channel expression in porcine and human renal pacemaker tissues

Isolated human uterine telocytes: immunocytochemistry and electrophysiology of T-type calcium channels

TRPC3 Overexpression Promotes the Progression of Inflammation-Induced Preterm Labor and Inhibits T Cell Activation

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