Anion Transport in Heart Hume, Joseph R; Duan, Dayue; Collier, Mei Lin ...
Physiological reviews,
01/2000, Letnik:
80, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Department of Physiology and Cell Biology, University of Nevada
School of Medicine, Reno, Nevada
Hume, Joseph R.,
Dayue Duan,
Mei Lin Collier,
Jun Yamazaki, and
Burton Horowitz.
Anion Transport in ...Heart. Physiol. Rev. 80: 31-81, 2000. Anion transport proteins in
mammalian cells participate in a wide variety of cell and intracellular
organelle functions, including regulation of electrical activity, pH,
volume, and the transport of osmolites and metabolites, and may even
play a role in the control of immunological responses, cell migration,
cell proliferation, and differentiation. Although significant progress
over the past decade has been achieved in understanding electrogenic
and electroneutral anion transport proteins in sarcolemmal and
intracellular membranes, information on the molecular nature and
physiological significance of many of these proteins, especially in the
heart, is incomplete. Functional and molecular studies presently
suggest that four primary types of sarcolemmal anion channels are
expressed in cardiac cells: channels regulated by protein kinase A
(PKA), protein kinase C, and purinergic receptors
( I Cl.PKA ); channels regulated by changes in cell
volume ( I Cl.vol ); channels activated by
intracellular Ca 2+ ( I Cl.Ca ); and
inwardly rectifying anion channels ( I Cl.ir ). In most animal species, I Cl.PKA is due to
expression of a cardiac isoform of the epithelial cystic fibrosis
transmembrane conductance regulator Cl channel. New
molecular candidates responsible for I Cl.vol ,
I Cl.Ca , and I Cl.ir
(ClC-3, CLCA1, and ClC-2, respectively) have recently been identified
and are presently being evaluated. Two isoforms of the band 3 anion
exchange protein, originally characterized in erythrocytes, are
responsible for Cl /HCO 3 exchange, and
at least two members of a large vertebrate family of electroneutral
cotransporters (ENCC1 and ENCC3) are responsible for
Na + -dependent Cl cotransport in heart. A
223-amino acid protein in the outer mitochondrial membrane of most
eukaryotic cells comprises a voltage-dependent anion channel. The
molecular entities responsible for other types of electroneutral anion
exchange or Cl conductances in intracellular membranes of
the sarcoplasmic reticulum or nucleus are unknown. Evidence of cardiac
expression of up to five additional members of the ClC gene family
suggest a rich new variety of molecular candidates that may underlie
existing or novel Cl channel subtypes in sarcolemmal and
intracellular membranes. The application of modern molecular biological
and genetic approaches to the study of anion transport proteins during
the next decade holds exciting promise for eventually revealing the
actual physiological, pathophysiological, and clinical significance of
these unique transport processes in cardiac and other mammalian cells.
ProTx-I peptide, a venom toxin of the tarantula Thrixopelma pruriens, has been reported to interact with voltage-gated ion channels. ProTx-I reduced Ba2+ currents through recombinant human T-type ...voltage-gated Ca2+ channels, Cav3.1 (hCav3.1), with roughly 160-fold more potency than through hCav3.2 channels. Chimeric channel proteins (hCav3.1/S3S4 and hCav3.2/ S3S4) were produced by exchanging fourteen amino acids in the hCav3.1 domain IV S3-S4 linker region and the corresponding region of hCav3.2 between each other. The ProTx-I sensitivity was markedly reduced in the hCav3.1/S3S4 chimera as compared to the original hCav3.1 channel, while the hCav3.2/S3S4 chimera exhibited greater ProTx-I sensitivity than the original hCav3.2 channel. These results suggest that the domain IV S3-S4 linker in the hCav3.1 channel may contain residues involved in the interaction of ProTx-I with T-type Ca2+ channels.
We reported that carbon monoxide (CO) generated through heme oxygenase (HO) inhibits mitogen-induced proliferation of vascular smooth muscle cells (VSMCs). We report that balloon injury induces HO-1, ...the stress-inducible isozyme of HO, in VSMCs and inhibits neointimal formation through the action of endogenous CO. Northern blot analysis and immunohistochemistry revealed that HO-1 is markedly induced in the media as early as 1 day after injury, whereas only a little expression was detected in the intact carotid artery. The neointimal proliferative changes were augmented or inhibited by the HO inhibitors or inducer, respectively, and effects of these interventions were not altered by suppression of endogenous nitric oxide (NO), if any. To elucidate the mechanisms by which HO controls the proliferative changes, effects of alterations in the HO reaction were examined by determining angiotensin II-elicited VSMC proliferation in vitro: the HO inducer attenuated and its inhibitor restored the proliferative response to angiotensin II (1 nM and 100 nM). Hemoglobin, a reagent trapping both NO and CO, but not met-hemoglobin, which can capture NO but not CO, augmented the proliferative response. These data suggest that endogenous CO serves as a protective factor that limits the excessive VSMC proliferation associated with vascular diseases.
Transient receptor potential ankyrin 1 (TRPA1) is a nonselective cation channel that is activated by a variety of stimuli and acts as a nociceptor. Mouse and human TRPA1 exhibit different reactivity ...to some stimuli, including chemicals such as menthol as well as cold stimuli. The cold sensitivity of TRPA1 in mammalian species is controversial. Here, we analyzed the reactivity of heterologously expressed canine TRPA1 as well as the mouse and human orthologs to menthol or cold stimulation in Ca2+-imaging experiments. Canine and human TRPA1 exhibited a similar response to menthol, that is, activation in a concentration-dependent manner, even at the high concentration range in contrast to the mouse ortholog, which did not respond to high concentration of menthol. In addition, the response during the removal of menthol was different; mouse TRPA1-expressing cells exhibited a typical response with a rapid and clear increase in Ca2+i (“off-response”), whereas Ca2+i in human TRPA1-expressing cells was dramatically decreased by the washout of menthol and Ca2+i in canine TRPA1-expressing cells was slightly decreased. Finally, canine TRPA1 as well as mouse and human TRPA1 were activated by cold stimulation (below 19°C–20°C). The sensitivity to cold stimulation differed between these species, that is, human TRPA1 activated at higher temperatures compared with the canine and mouse orthologs. All of the above responses were suppressed by the selective TRPA1 inhibitor HC-030031. Because the concentration-dependency and “off-response” of menthol as well as the cold sensitivity were not uniform among these species, studies of canine TRPA1 might be useful for understanding the species-specific functional properties of mammalian TRPA1.
Cl−-permeable channels and transporters expressed on the cell membranes of various mammalian cell types play pivotal roles in the transport of electrolytes and water, pH regulation, cell volume and ...membrane excitability, and are therefore expected to be useful molecular targets for drug discovery. Both TMEM16A (a possible candidate for Ca2+-regulated Cl− channels recently identified) and cystic fibrosis transmembrane conductance regulator (CFTR) (or cAMP-regulated Cl− channels) have been known to be involved in Cl− secretion and reabsorption in the rat salivary gland. Crosstalk between two types of regulatory pathways through these two types of channels has also been described. Previously, we demonstrated that CLCA, a Ca2+-activated Cl− channel modulator, was involved in Cl− absorption in rat salivary ducts. In addition to Ca2+, basal NF-κB activity in a mouse keratinocyte line was shown to be involved in the transcriptional regulation of CLCA. Conversely, a truncated isoform of CLCA was found in undifferentiated epithelial cells present in the rat epidermal basal layers. Under regulation by Ca2+ and PKC, the surface expression of β1-integrin and cell adhesion were decreased in the CLCA-overexpressing cells. Knockdown of this isoform elevated the expression of β1-integrin in rat epidermis in vivo. These results indicate that the specific differentiation-dependent localization of CLCA, and transcriptional regulation through Ca2+, are likely to affect ion permeability and the adhesive potential of epithelial cells. In summary, these types of Cl− channels and their modulators may function in a coordinated manner in regulating the functions of epithelial cells under different physiological conditions.
Cl(-)-permeable channels and transporters expressed on the cell membranes of various mammalian cell types play pivotal roles in the transport of electrolytes and water, pH regulation, cell volume and ...membrane excitability, and are therefore expected to be useful molecular targets for drug discovery. Both TMEM16A (a possible candidate for Ca(2+)-regulated Cl(-) channels recently identified) and cystic fibrosis transmembrane conductance regulator (CFTR) (or cAMP-regulated Cl(-) channels) have been known to be involved in Cl(-) secretion and reabsorption in the rat salivary gland. Crosstalk between two types of regulatory pathways through these two types of channels has also been described. Previously, we demonstrated that CLCA, a Ca(2+)-activated Cl(-) channel modulator, was involved in Cl(-) absorption in rat salivary ducts. In addition to Ca(2+), basal NF-κB activity in a mouse keratinocyte line was shown to be involved in the transcriptional regulation of CLCA. Conversely, a truncated isoform of CLCA was found in undifferentiated epithelial cells present in the rat epidermal basal layers. Under regulation by Ca(2+) and PKC, the surface expression of β1-integrin and cell adhesion were decreased in the CLCA-overexpressing cells. Knockdown of this isoform elevated the expression of β1-integrin in rat epidermis in vivo. These results indicate that the specific differentiation-dependent localization of CLCA, and transcriptional regulation through Ca(2+), are likely to affect ion permeability and the adhesive potential of epithelial cells. In summary, these types of Cl(-) channels and their modulators may function in a coordinated manner in regulating the functions of epithelial cells under different physiological conditions.
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