Rapid nongenomic responses to steroids include modulation of ion channel activities on the cell membrane of target cells, but little is known about the molecular mechanisms involved. In this paper we investigate the mechanisms underlying the combined action of the secosteroid hormone 1alpha,25-dihydroxyvitamin D3 [1alpha,25(OH)(2)D3] on three different ion channel types in rat osteoblasts, which include a voltage-gated L-type Ca(2+) channel, a mechanosensitive Cl(-) channel, and a stretch-activated cation (SA-Cat) channel. We found that physiological nanomolar concentrations of 1alpha,25(OH)(2)D3 rapidly modify the overall electrical activity of the membrane in ROS 17/2.8 cells. 1alpha,25(OH)(2)D3 increases the osteoblast L-type Ca(2+) channel activity at low depolarizing voltages in a fashion similar to the 1,4-dihydropyridine (DHP) agonist Bay K8644. At highly depolarizing potentials 1alpha,25(OH)(2)D3 potentiates volume-sensitive Cl(-) currents through mechanisms that may involve a putative membrane receptor. We show for the first time that 1alpha,25(OH)(2)D3 also increases inward currents through SA-Cat channels at positive membrane voltages in a dose-dependent manner. Contrary to our expectations, the stereoisomer 1beta,25(OH)(2)D3, which suppresses 1alpha,25(OH)(2)D3 activation of osteoblast Cl(-) currents, mimicked 1alpha,25(OH)(2)D3 agonist effects on Ca(2+) and SA-Cat channel activities. Cyclic AMP is involved in 1alpha,25(OH)(2)D3 effects on both Ca(2+) and SA-Cat channels, but not in Cl(-) channels. We conclude that 1alpha,25(OH)(2)D3 rapid effects on ion channel activities in ROS 17/2.8 cells occur through multiple mechanisms that, on the one hand, involve a possible direct interaction with the L-type Ca(2+) channel molecule and, on the other hand, molecular pathways that may include a putative membrane receptor.

Download full-text PDF

Source
http://dx.doi.org/10.1016/s8756-3282(03)00162-5DOI Listing

Publication Analysis

Top Keywords

ion channel
16
channel activities
16
l-type ca2+
12
ca2+ channel
12
channel
10
molecular mechanisms
8
three ion
8
sa-cat channel
8
1alpha25oh2d3
8
ros 17/28
8

Similar Publications

The present article deals with the modulation of oscillatory electroosmotic flow (EOF) and solute dispersion across a nanochannel filled with an electrolyte solution surrounded by a layer of a dielectric liquid. The dielectric permittivity of the liquid layer adjacent to supporting rigid walls is taken to be lower than that of the electrolyte solution. Besides, the aforesaid liquid layer may bear additional mobile charges, , free lipid molecules, charged surfactant molecules , which in turn lead to a nonzero charge along the liquid-liquid interface.

View Article and Find Full Text PDF

Piezo1 Enhances Macrophage Phagocytosis and Pyrin Activation to Ameliorate Fungal Keratitis.

Invest Ophthalmol Vis Sci

January 2025

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou, China.

Purpose: Fungal keratitis (FK) remains a treatment challenge, necessitating new therapeutic targets. Piezo1, a mechanosensitive ion channel, regulates calcium signaling and immune cell function. This study investigates its role in macrophage-mediated antifungal responses in FK.

View Article and Find Full Text PDF

Purpose: The major cardiac voltage-gated sodium channel Na1.5 (I) is essential for cardiac action potential initiation and subsequent propagation. Compound Chinese medicine Wenxin Keli (WXKL) has been shown to suppress arrhythmias and heart failure.

View Article and Find Full Text PDF

The sensation of sng (pronounced/səŋ/, the Romanization form of or soreness in Taiwanese Southern Min) associated with a composite of unique sensations, is a novel phenotype for acupoint stimulation. It is perceived by test participants but also by experienced practitioners as a sensation of "taking the bait" (by fish when fishing), a characteristic heavy and tight sensation from the needle. Here, we propose that sng is a powerful biomarker for associated with successful manual acupuncture.

View Article and Find Full Text PDF

Ultramicroporous Tröger's Base Framework Membranes With Ionized Sub-nanochannels for Efficient Acid/Alkali Recovery.

Adv Sci (Weinh)

January 2025

Research Center for Membrane and Film Technology, Department of Chemical Science and Engineering, Kobe University, Kobe, 6500034, Japan.

Membrane technology holds significant potential for the recovery of acids and alkalis from industrial wastewater systems, with ion exchange membranes (IEMs) playing a crucial role in these applications. However, conventional IEMs are limited to separating only monovalent cations or anions, presenting a significant challenge in achieving concomitant H⁺/OH⁻ permselectivity for simultaneous acid and alkali recovery. To address this issue, the charged microporous polymer framework membranes are developed, featuring rigid Tröger's Base network chains constructed through a facile sol-gel process.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!