T-type Ca2+ channels in non-vascular smooth muscles

Fry, CH; Sui, Guiping; Wu, Changhao

doi:10.1016/j.ceca.2006.04.027

Cited by 32 publications

(24 citation statements)

References 80 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may be that Ca 2+ influx through T‐type Ca 2+ channels in myocytes is more important for functions of Ca 2+ unrelated to contractility such as cellular proliferation or migration. In this respect, myocytes from mouse jejunum are similar to other smooth muscles [2, 42] although there does appear to be role for α 1H Ca 2+ channel subunits in controlling relaxation of coronary smooth muscle [43].…”

Section: Discussionmentioning

confidence: 99%

The α_1H Ca²⁺ channel subunit is expressed in mouse jejunal interstitial cells of Cajal and myocytes

Gibbons

Strege

Sha

et al. 2009

J Cellular Molecular Medi

View full text Add to dashboard Cite

T-type Ca2+ currents have been detected in cells from the external muscular layers of gastrointestinal smooth muscles and appear to contribute to the generation of pacemaker potentials in interstitial cells of Cajal from those tissues. However, the Ca2+ channel α subunit responsible for these currents has not been determined. We established that the α subunit of the α1H Ca2+ channel is expressed in single myocytes and interstitial cells of Cajal using reverse transcription and polymerase chain reaction from whole tissue, laser capture microdissected tissue and single cells isolated from the mouse jejunum. Whole-cell voltage clamp recordings demonstrated that a nifedipine and Cd2+ resistant, mibefradil-sensitive current is present in myocytes dissociated from the jejunum. Electrical recordings from the circular muscle layer demonstrated that mibefradil reduced the frequency and initial rate of rise of the electrical slow wave. Gene targeted knockout of both alleles of the cacna1h gene, which encodes the α1H Ca2+ channel subunit, resulted in embryonic lethality because of death of the homozygous knockouts prior to E13.5 days in utero. We conclude that a channel with the pharmacological and molecular characteristics of the α1H Ca2+ channel subunit is expressed in interstitial cells of Cajal and myocytes from the mouse jejunum, and that ionic conductances through the α1H Ca2+ channel contribute to the upstroke of the pacemaker potential. Furthermore, the survival of mice that do not express the α1H Ca2+ channel protein is dependent on the genetic background and targeting approach used to generate the knockout mice.

show abstract

Section: Discussionmentioning

confidence: 99%

The α_1H Ca²⁺ channel subunit is expressed in mouse jejunal interstitial cells of Cajal and myocytes

Gibbons

Strege

Sha

et al. 2009

J Cellular Molecular Medi

View full text Add to dashboard Cite

show abstract

“…T-type Ca 2+ -currents serve as pacemakers of rhythmic activity in a diverse array of cell types [20][21][22] . These channels are activated by relatively small membrane depolarizations, but then also rapidly inactivate 15;16;20 .…”

Section: (2) Regulation Of Cytosolic Levels Of [Ca 2+ ] (21) Generalmentioning

confidence: 99%

“…Transient receptor potential (TRP) channels are a family of voltage-independent Ca 2+channels which can respond to a diverse array of stimuli, including internal Ca 2+ -store depletion, stretch, and osmotic stress 19 . One sub-group, the vanilloid or TRPV channels, generally respond to temperature and a variety of ligands which are perceived as hot, including vanilla, cinnamon, and capsaicin.T-type Ca 2+ -currents serve as pacemakers of rhythmic activity in a diverse array of cell types [20][21][22] . These channels are activated by relatively small membrane depolarizations, but then also rapidly inactivate 15;16;20 .…”

mentioning

confidence: 99%

Calcium Homeostasis and Ionic Mechanisms in Pulmonary Fibroblasts

Janssen

Mukherjee

Ask

2015

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Fibroblasts are key cellular mediators of many chronic interstitial lung diseases, including idiopathic pulmonary fibrosis, scleroderma, sarcoidosis, drug-induced interstitial lung disease, and interstitial lung disease in connective tissue disease. A great deal of effort has been expended to understand the signaling mechanisms underlying the various cellular functions of fibroblasts. Recently, it has been shown that Ca(2+) oscillations play a central role in the regulation of gene expression in human pulmonary fibroblasts. However, the mechanisms whereby cytosolic [Ca(2+)] are regulated and [Ca(2+)] oscillations transduced are both poorly understood. In this review, we present the general concepts of [Ca(2+)] homeostasis, of ionic mechanisms responsible for various Ca(2+) fluxes, and of regulation of gene expression by [Ca(2+)]. In each case, we then also summarize the original findings that pertain specifically to pulmonary fibroblasts. From these data, we propose an overall signaling cascade by which excitation of the fibroblasts triggers pulsatile release of internally sequestered Ca(2+), which, in turn, activates membrane conductances, including voltage-dependent Ca(2+) influx pathways. Collectively, these events produce recurring Ca(2+) oscillations, the frequency of which is transduced by Ca(2+)-dependent transcription factors, which, in turn, orchestrate a variety of cellular events, including proliferation, synthesis/secretion of extracellular matrix proteins, autoactivation (production of transforming growth factor-β), and transformation into myofibroblasts. That unifying hypothesis, in turn, allows us to highlight several specific cellular targets and therapeutic intervention strategies aimed at controlling unwanted pulmonary fibrosis. The relationships between Ca(2+) signaling events and the unfolded protein response and apoptosis are also explored.

show abstract

“…Two types of VDCCs (L-type and T-type) have been identified in DSM cells similar to other smooth muscle cell types (1,13,48). The lower threshold of activation for the T-type VDCCs determines that they are active at the resting membrane potential of approximately Ϫ40 mV and could regulate DSM excitability.…”

mentioning

confidence: 99%

Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca²⁺ channels

Malysz

Afeli

Provence

et al. 2014

American Journal of Physiology-Cell Physiology

View full text Add to dashboard Cite

Malysz J, Afeli SA, Provence A, Petkov GV. Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca 2ϩ channels. Am J Physiol Cell Physiol 306: C45-C58, 2014. First published October 23, 2013 doi:10.1152/ajpcell.00047.2013.-Mechanisms underlying ethanol (EtOH)-induced detrusor smooth muscle (DSM) relaxation and increased urinary bladder capacity remain unknown. We investigated whether the large conductance Ca 2ϩ -activated K ϩ (BK) channels or L-type voltage-dependent Ca 2ϩ channels (VDCCs), major regulators of DSM excitability and contractility, are targets for EtOH by patch-clamp electrophysiology (conventional and perforated whole cell and excised patch single channel) and isometric tension recordings using guinea pig DSM cells and isolated tissue strips, respectively. EtOH at 0.3% vol/vol (ϳ50 mM) enhanced whole cell BK currents at ϩ30 mV and above, determined by the selective BK channel blocker paxilline. In excised patches recorded at ϩ40 mV and ϳ300 nM intracellular Ca 2ϩ concentration ([Ca 2ϩ ]), EtOH (0.1-0.3%) affected single BK channels (mean conductance ϳ210 pS and blocked by paxilline) by increasing the open channel probability, number of open channel events, and open dwell-time constants. The amplitude of single BK channel currents and unitary conductance were not altered by EtOH. Conversely, at ϳ10 M but not ϳ2 M intracellular [Ca 2ϩ ], EtOH (0.3%) decreased the single BK channel activity. EtOH (0.3%) affected transient BK currents (TBKCs) by either increasing frequency or decreasing amplitude, depending on the basal level of TBKC frequency. In isolated DSM strips, EtOH (0.1-1%) reduced the amplitude and muscle force of spontaneous phasic contractions. The EtOH-induced DSM relaxation, except at 1%, was attenuated by paxilline. EtOH (1%) inhibited L-type VDCC currents in DSM cells. In summary, we reveal the involvement of BK channels and L-type VDCCs in mediating EtOHinduced urinary bladder relaxation accommodating alcohol-induced diuresis. smooth muscle; patch-clamp; contractility; detrusor; alcohol URINARY BLADDER FUNCTION DEPENDS on the contractile status of detrusor smooth muscle (DSM) cells. DSM relaxation allows for bladder expansion during urine storage, whereas its contraction, coupled with the opening of the bladder sphincter, permits urine voiding (3). Multiple ion channels and receptors are expressed in DSM cells regulating bladder function. Among them, the large-conductance voltage-and Ca 2ϩ -activated K ϩ channels (also known as BK, Slo, or K Ca 1.1 channels) and L-type voltage-dependent Ca 2ϩ channels (VDCCs) are recognized as key regulators of excitability and contractility of DSM (44). Supporting data, provided for DSM studies using rat, guinea pig, mouse, and importantly human tissues and cells (5,17,18,22,24,25,46), demonstrate the role of BK channels in the regulation of the resting membrane potential, modulation of the repolarization phase of DSM action potentials, and generation of spontaneous transient BK currents (TBKCs)...

show abstract

T-type Ca2+ channels in non-vascular smooth muscles

Cited by 32 publications

References 80 publications

The α_1H Ca²⁺ channel subunit is expressed in mouse jejunal interstitial cells of Cajal and myocytes

The α_1H Ca²⁺ channel subunit is expressed in mouse jejunal interstitial cells of Cajal and myocytes

Calcium Homeostasis and Ionic Mechanisms in Pulmonary Fibroblasts

Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca²⁺ channels

Contact Info

Product

Resources

About

T-type Ca2+ channels in non-vascular smooth muscles

Cited by 32 publications

References 80 publications

The α1H Ca2+ channel subunit is expressed in mouse jejunal interstitial cells of Cajal and myocytes

The α1H Ca2+ channel subunit is expressed in mouse jejunal interstitial cells of Cajal and myocytes

Calcium Homeostasis and Ionic Mechanisms in Pulmonary Fibroblasts

Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca2+ channels

Contact Info

Product

Resources

About

The α_1H Ca²⁺ channel subunit is expressed in mouse jejunal interstitial cells of Cajal and myocytes

The α_1H Ca²⁺ channel subunit is expressed in mouse jejunal interstitial cells of Cajal and myocytes

Ethanol-mediated relaxation of guinea pig urinary bladder smooth muscle: involvement of BK and L-type Ca²⁺ channels