Article

Known calcium channel alpha1 subunits can form low threshold small conductance channels with similarities to native T-type channels.

Department of Pharmacology, University College London, United Kingdom.
Neuron (impact factor: 14.74). 03/1998; 20(2):341-51.
Source: PubMed

ABSTRACT Native T-type voltage-dependent calcium channels are low voltage-activated and have a small single channel conductance of 5-8 pS, which distinguishes them from any known cloned calcium channels whose conductances are 12-25 pS. Here, we show that when alpha1B, alpha1E, or alpha1C are expressed in COS7 cells, which contain no endogenous calcium channel subunits or calcium channels, they each exhibit a 4-7 pS channel as well as a large conductance channel. At low depolarizations, or when the alpha1 subunit is expressed in the absence of auxiliary alpha2-delta or beta subunits, the small conductance channels are seen alone, and their biophysical properties, including voltage dependence and kinetics of activation and inactivation, are very similar to native T-type calcium channels.

0 0
 · 
0 Bookmarks
 · 
16 Views
  • Source
    Article: The Ca(v)1.4 calcium channel: more than meets the eye.
    Clinton J Doering, Jean B Peloquin, John E McRory
    [show abstract] [hide abstract]
    ABSTRACT: Ca(v)1.4 channels are the latest calcium channels to be described in the literature. Originally identified in 1997 from the human genome project, several reports have since been published describing mutations in the CACNA1F gene encoding Ca(v)1.4 channels, and implicated these mutations in human disorders such as X-linked cone rod dystrophy (CORDX3) and incomplete X-linked congenital stationary night blindness type 2 (CSNB2). The gene was subsequently cloned and expressed in heterologous expression systems beginning in 2003, and many of the mutations linked to CSNB2 have been tested. Here, we review literature describing the discovery of the CACNA1F gene, its tissue expression profile, alternative splicing events, and biophysical and pharmacological characteristics of the channel in various expression systems. Channel biophysics are also compared to those obtained from recordings made from vertebrate photoreceptors, suggesting that these studies may have been describing Ca(v)1.4 channels in native cells.
    Channels (Austin, Tex.) 02/2007; 1(1):3-10. · 1.91 Impact Factor
  • Article: Molecular basis of the T- and L-type Ca2+ currents in canine Purkinje fibres.
    Barbara Rosati, Wen Dun, Masanori Hirose, Penelope A Boyden, David McKinnon
    [show abstract] [hide abstract]
    ABSTRACT: This study examines the molecular basis for the T-type and L-type Ca(2+) currents in canine Purkinje cells. The I(CaT) in Purkinje cells was completely suppressed by 200 nM kurtoxin, a specific blocker of both Ca(v)3.1 and Ca(v)3.2 channels. Since only Ca(v)3.2 mRNA is expressed at high levels in Purkinje fibres, being approximately 100-fold more abundant than either Ca(v)3.1 or Ca(v)3.3 mRNAs, it is concluded that the Ca(v)3.2 gene encodes the bulk of the T-type Ca(2+) channels in canine Purkinje cells. This conclusion is consistent with the sensitivity of the current to blockade by Ni(2+) ions (K(D) = 32 microM). For L-type channels, Ca(v)1.2 mRNA was most abundant in Purkinje fibres but a significant level of Ca(v)1.3 mRNA expression was also found. A comparison of the sensitivity to blockade by isradipine of the L-type currents in Purkinje cells and ventricular epicardial myocytes, which only express Ca(v)1.2, suggests that the Ca(v)1.3 channels make, at most, a minor contribution to the L-type current in canine Purkinje cells.
    The Journal of Physiology 04/2007; 579(Pt 2):465-71. · 4.72 Impact Factor
  • Source
    Article: Voltage-dependent calcium channels in mammalian spermatozoa revisited.
    Susan Benoff, Charles C Chu, Joel L Marmar, Rebecca Z Sokol, Leslie O Goodwin, Ian R Hurley
    [show abstract] [hide abstract]
    ABSTRACT: The last few years have seen an explosion in the number of voltage-dependent ion channel sequences detected in sperm and testes. The complex structural paradigm of these channels is now known to include a pore-forming alpha1 subunit(s) whose electrophysiological properties are modulated by an intracellular beta subunit, a disulfide-linked complex of a membrane-spanning delta subunit with an extracellular alpha2 subunit, and a transmembrane gamma subunit. Many of these are alternatively spliced. Furthermore, the known number of genes coding each subtype has expanded significantly (10 alpha1, 4 beta, 4 alpha2delta, 8 gamma). Recently, the CatSper gene family has been characterized based on similarity to the voltage-dependent calcium channel alpha1 subunit. From among this multiplicity, a wide cross-section is active in sperm, including many splice variants. For example, expression of the various alpha1 subunits appears strictly localized in discrete domains of mature sperm, and seems to control distinct physiological roles such as cellular signaling pathways. These include alpha1 alternative splicing variants that are regulated by ions passed by channels in developing sperm. Various combinations of ion channel sequence variants have been studies in research models and in a variety of human diseases, including male infertility. For example, rats that are genetically resistant to testes damage by lead seem to respond to lead ions by increasing alpha1 alternative splicing. In contrast, in varicocele-associated male infertility, the outcome from surgical correction correlates with suppression of alpha1 alternative splicing, Ion channel blockers remain attractive model contraceptive drugs because of their ability to modulate cholesterol levels. However, the large number of sperm ion channel variants shared with other cell types make ion channels less attractive targets for male contraceptive development than a few years ago. In this review, the genetics, structure and function of voltage-dependent calcium channels and related CatSper molecules will be discussed, and several practical clinical applications associated with these channels will be reported.
    Frontiers in Bioscience 02/2007; 12:1420-49. · 3.52 Impact Factor

Show more

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

4-7 pS channel
 
alpha1 subunit
 
alpha1B
 
alpha1C
 
alpha1E
 
beta subunits
 
calcium channels
 
cloned calcium channels
 
COS7 cells
 
endogenous calcium channel subunits
 
large conductance channel
 
native T-type calcium channels
 
Native T-type voltage-dependent calcium channels
 
small conductance channels
 
small single channel conductance
 
voltage dependence