Contribution of transient receptor potential vanilloid 1 (TRPV1) channel to cholinergic contraction of rat bladder smooth muscle.

Transient receptor potential vanilloid 1 (TRPV1) is a calcium-permeable ion channel that is gated by the pungent constituent of red chili pepper, capsaicin, and by related chemicals from the group of vanilloids, in addition to noxious heat. It is expressed mostly in sensory neurons to act as a detector of painful stimuli produced by pungent chemicals and high temperatures. Although TRPV1 is also found outside the sensory nervous system, its expression and function in the bladder detrusor smooth muscle (DSM) remain controversial.

Temperature-dependent contractility of rat tunica dartos muscle: Contribution of cold, menthol-sensitive TRPM8.

Tunica dartos smooth muscle (TDSM) lies beneath the scrotal skin, and its contraction leads to scrotum wrinkling upon cooling. However, neither the nature of TDSM cold-sensitivity nor the underlying molecular sensors are well understood. Here we have investigated the role of cold/menthol-sensitive TRPM8 channel in TDSM temperature-dependent contractility.

Impairment of urinary bladder mechanical properties in rat model of type 2 diabetes.

Aims: The urinary bladder is a mechanosensitive organ that accumulates, stores, and expels considerable amounts of fluid. While the neuronal bladder control via the CNS is well defined, the data on the mechanisms of local mechanical sensitivity of the bladder wall are either insufficient or contradictory. Here we compared the mechanical properties of bladder wall of normal rats and rats with modeled type 2 diabetes (T2D).

Induction of A549 Nonsmall-Cell Lung Cancer Cells Proliferation by Photoreleased Nicotine.

Caged compounds comprise the group of artificially synthesized, light-sensitive molecules that enable in situ derivation of biologically active constituents capable of affecting cells, tissues and/or biological processes upon exposure to light. Ruthenium-bispyridine (RuBi) complexes are photolyzed by biologically harmless visible light. In the present study, we show that RuBi-caged nicotine can be used as a source of free nicotine to induce proliferation of A549 nonsmall-cell lung cancer (NSCLC) cells by acting on nicotinic acetylcholine receptors expressed in these cells.

Beyond Neuronal Heat Sensing: Diversity of TRPV1 Heat-Capsaicin Receptor-Channel Functions.

Transient receptor potential vanilloid 1 (TRPV1) is a calcium-permeable ion channel best known for its ability to be gated by the pungent constituent of red chili pepper, capsaicin, and related chemicals from the group of vanilloids as well as by noxious heat. As such, it is mostly expressed in sensory neurons to act as a detector of painful stimuli produced by pungent chemicals and high temperatures. Its activation is also sensitized by the numerous endogenous inflammatory mediators and second messengers, making it an important determinant of nociceptive signaling.

Alterations in detrusor contractility in rat model of bladder cancer.

Urinary incontinence of idiopathic nature is a common complication of bladder cancer, yet, the mechanisms underlying changes in bladder contractility associated with cancer are not known. Here by using tensiometry on detrusor smooth muscle (DSM) strips from normal rats and rats with bladder cancer induced by known urothelial carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), we show that bladder cancer is associated with considerable changes in DSM contractility. These changes include: (1) decrease in the amplitude and frequency of spontaneous contractions, consistent with the decline of luminal pressures during filling, and detrusor underactivity; (2) diminution of parasympathetic DSM stimulation mainly at the expense of m-cholinergic excitatory transmission, suggestive of difficulty in bladder emptying and weakening of urine stream; (3) strengthening of TRPV1-dependent afferent limb of micturition reflex and TRPV1-mediated local contractility, promoting urge incontinence; (4) attenuation of stretch-dependent, TRPV4-mediated spontaneous contractility leading to overflow incontinence.

Testosterone-androgen receptor: The steroid link inhibiting TRPM8-mediated cold sensitivity.

Recent studies have revealed gender differences in cold perception, and pointed to a possible direct action of testosterone (TST) on the cold-activated TRPM8 (Transient Receptor Potential Melastatin Member 8) channel. However, the mechanisms by which TST influences TRPM8-mediated sensory functions remain elusive. Here, we show that TST inhibits TRPM8-mediated mild-cold perception through the noncanonical engagement of the Androgen Receptor (AR).

Ca channel-forming ORAI proteins: cancer foes or cancer allies?

The ORAI family of ion channel-forming proteins in mammals includes three members, ORAI1, ORAI2 and ORAI3, encoded by homologous genes. Of these proteins the ORAI1 one received major attention as plasma membrane constituent of store-operated calcium entry (SOCE) in non-excitable cells. The functional significance of two other proteins, ORAI2 and ORAI3, is much less defined, although both of them participate to various extends in cell-specific modulation of SOCE as well as in supporting some of the store-independent calcium entry mechanisms.

Impairment of cholinergic bladder contractility in rat model of type I diabetes complicated by cystitis: Contribution of neurotransmitter-degrading ectoenzymes.

Parasympathetic regulation of urinary bladder contractions primarily involves acetylcholine release and activation of detrusor smooth muscle (DSM) muscarinic acetylcholine (mACh) receptors. Co-release of ATP and activation of DSM purinergic P2X1-receptors may participate as well in some species. Both types of neuromuscular transmission (NMT) are impaired in diabetes, however, which factors may contribute to such impairment remains poorly understood.

A-Kinase-Anchoring Protein (AKAP150) is expressed in Astrocytes and Upregulated in Response to Ischemia.

A-kinase-anchoring proteins, AKAPs, are scaffolding proteins that associate with kinases and phosphatases, and direct them to a specific submembrane site to coordinate signaling events. AKAP150, a rodent ortholog of human AKAP79, has been extensively studied in neurons, but very little is known about the localization and function of AKAP150 in astrocytes, the major cell type in brain. Thus, in this study, we assessed the localization of AKAP150 in astrocytes and elucidated its role during physiological and ischemic conditions.

Ion Channels in Cancer: Are Cancer Hallmarks Oncochannelopathies?

Genomic instability is a primary cause and fundamental feature of human cancer. However, all cancer cell genotypes generally translate into several common pathophysiological features, often referred to as cancer hallmarks. Although nowadays the catalog of cancer hallmarks is quite broad, the most common and obvious of them are 1) uncontrolled proliferation, 2) resistance to programmed cell death (apoptosis), 3) tissue invasion and metastasis, and 4) sustained angiogenesis.

TRPV1 alterations in urinary bladder dysfunction in a rat model of STZ-induced diabetes.

Aims: More than half of diabetic patients experience voiding disorder termed diabetic urinary bladder dysfunction (DBD). Here we have investigated how the alterations in transient receptor potential vanilloid 1 (TRPV1) ion channel expressed in bladder-innervating afferents may contribute to DBD pathogenesis.

Main Methods: The rat model of streptozotocin (STZ)-induced diabetes was used.

Myorelaxant action of fluorine-containing pinacidil analog, flocalin, in bladder smooth muscle is mediated by inhibition of L-type calcium channels rather than activation of KATP channels.

Flocalin (FLO) is a new ATP-sensitive K(+) (KATP) channel opener (KCO) derived from pinacidil (PIN) by adding fluorine group to the drug's structure. FLO acts as a potent cardioprotector against ischemia-reperfusion damage in isolated heart and whole animal models primarily via activating cardiac-specific Kir6.2/SUR2A KATP channels.

TRPA1-dependent regulation of bladder detrusor smooth muscle contractility in normal and type I diabetic rats.

TRPA1 is a Ca(2+)-permeable cation channel that is activated by painful low temperatures (<17°C), irritating chemicals, reactive metabolites and mediators of inflammation. In the bladder TRPA1 is predominantly expressed in sensory afferent nerve endings, where it mediates sensory transduction. The contractile effect of its activation on detrusor smooth muscle (DSM) is explained by the release from sensory afferents of inflammatory factors - tachykinins and prostaglandins, which cause smooth muscle cell contraction.

Compensatory reduction of Cav3.1 expression in thalamocortical neurons of juvenile rats of WAG/Rij model of absence epilepsy.

Absence seizures are the non-convulsive form of generalized epilepsy critically dependent on T-type calcium channels (Cav3) in thalamic neurons. In humans, absences accompany only childhood or adolescent epileptic syndromes--though in its polygenic rat models WAG/Rij and GAERS the opposite developmental pattern is observed. Hereby we address this issue by transcriptional and functional study of thalamic Cav3 in juvenile (i.

Assessment of gold nanoparticle effect on prostate cancer LNCaP cells.

Unlabelled: In recent years gold nanoparticles (AuNPs) have received considerable attention for various biomedical applications including diagnostics and targeted drug delivery. However, more research is still needed to characterize such aspects of their use in clinical oncology as permeability, retention and functional effect on tumor cells.

Aims: This study was designed to describe the effect of non-functionalized AuNPs on LNCaP prostate cancer cells growth.

Disrupting the dynamic equilibrium of ORAI channels determines the phenotype of malignant cells.

We recently unraveled a finely tuned oncogenic mechanism in which genetic and tumor microenvironment alterations act together on a crucial calcium signaling pathway. This pathway involves an interconnected equilibrium of calcium channels functioning like a binary star system in which ORAI1 homomers and ORAI1/3 heteromers are two companion stars under the influence of each other that orbit around the cancer hallmarks of apoptosis resistance and enhanced proliferation.

Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes.

Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening.

Remodeling of channel-forming ORAI proteins determines an oncogenic switch in prostate cancer.

ORAI family channels have emerged as important players in malignant transformation, yet the way in which they reprogram cancer cells remains elusive. Here we show that the relative expression levels of ORAI proteins in prostate cancer are different from that in noncancerous tissue. By mimicking ORAI protein remodeling observed in primary tumors, we demonstrate in in vitro models that enhanced ORAI3 expression favors heteromerization with ORAI1 to form a novel channel.

Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes.

Background And Purpose: The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes.

Experimental Approach: Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes.

Key Results: In the presence of 1-10 μM AEA, suppression of both Na(+) and L-type Ca(2+) channels was observed.

Effects of endogenous cannabinoid anandamide on cardiac Na⁺/Ca²⁺ exchanger.

Endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) has been shown to cause negative inotropic and antiarrhythmic effects in ventricular myocytes. In this study, using whole-cell patch clamp technique, we have investigated the effects of AEA on cardiac Na(+)/Ca(2+) exchanger (NCX1)-mediated currents. AEA suppressed NCX1 with an IC50 value of 4.

Remodelling of Ca2+ transport in cancer: how it contributes to cancer hallmarks?

Cancer involves defects in the mechanisms underlying cell proliferation, death and migration. Calcium ions are central to these phenomena, serving as major signalling agents with spatial localization, magnitude and temporal characteristics of calcium signals ultimately determining cell's fate. Cellular Ca(2+) signalling is determined by the concerted action of a molecular Ca(2+)-handling toolkit which includes: active energy-dependent Ca(2+) transporters, Ca(2+)-permeable ion channels, Ca(2+)-binding and storage proteins, Ca(2+)-dependent effectors.

Effects of endogenous cannabinoid anandamide on excitation-contraction coupling in rat ventricular myocytes.

A role for anandamide (N-arachidonoyl ethanolamide; AEA), a major endocannabinoid, in the cardiovascular system in various pathological conditions has been reported in earlier reports. In the present study, the effects of AEA on contractility, Ca2+ signaling, and action potential (AP) characteristics were investigated in rat ventricular myocytes. Video edge detection was used to measure myocyte shortening.

Models of calcium permeation through T-type channels.

Ca(2+) entry is indispensable part of intracellular Ca(2+) signaling, which is vital for most of cellular functions. Low voltage-activated (LVA or T-type) calcium channels belong to the family of voltage-gated calcium channels (VGCCs) which provide Ca(2+) entry in response to membrane depolarization. VGCCs are generally characterized by exceptional Ca(2+) selectivity combined with high permeation rate, thought to be determined by the presence in their selectivity filter of a versatile Ca(2+) binding site formed by four glutamate residues (EEEE motif).