Calcium sensitivity of BK-type KCa channels determined by a separable domain

Wei, Aguan; Solaro, Christopher R.; Lingle, Christopher J.; Salkoff, Lawrence

doi:10.1016/0896-6273(94)90034-5

Cited by 237 publications

(287 citation statements)

References 30 publications

Supporting

Mentioning

257

Contrasting

Order By: Relevance

“…The mSlo ␣-subunit (accession number L16912; Butler et al, 1993) used in these experiments was identical to that used in previous work from this lab (mbr5; Wei et al, 1994;Saito et al, 1997). Specifically, we used a construct containing no insert at the mammalian splice site 2 (Tseng-Crank et al, 1994).…”

Section: Isolation Of Cdna Clonesmentioning

confidence: 99%

“…First the plasmids were linearized with an appropriate enzyme (SalI for mSlo and MluI for ␤-constructs). T3 (mSlo construct; Wei et al, 1994) or Sp6 (all ␤-related constructs) RNA polymerases were used for run-off transcription (X ia et al, 1998b). Total cRNA (0.1-0.5 ng) was injected into stage IV Xenopus oocytes that were harvested the day before.…”

Section: Isolation Of Cdna Clonesmentioning

confidence: 99%

See 1 more Smart Citation

Molecular Basis for the Inactivation of Ca²⁺- and Voltage-Dependent BK Channels in Adrenal Chromaffin Cells and Rat Insulinoma Tumor Cells

Xia¹,

Ding²,

1999

View full text Add to dashboard Cite

Large-conductance Ca 2ϩ -and voltage-dependent potassium (BK) channels exhibit functional diversity not explained by known splice variants of the single Slo ␣-subunit. Here we describe an accessory subunit (␤3) with homology to other ␤-subunits of BK channels that confers inactivation when it is coexpressed with Slo. Message encoding the ␤3 subunit is found in rat insulinoma tumor (RINm5f) cells and adrenal chromaffin cells, both of which express inactivating BK channels. Channels resulting from coexpression of Slo ␣ and ␤3 subunits exhibit properties characteristic of native inactivating BK channels. Inactivation involves multiple cytosolic, trypsin-sensitive domains. The time constant of inactivation reaches a limiting value ϳ25-30 msec at Ca 2ϩ of 10 M and positive activation potentials. Unlike Shaker N-terminal inactivation, but like native inactivating BK channels, a cytosolic channel blocker does not compete with the native inactivation process. Finally, the ␤3 subunit confers a reduced sensitivity to charybdotoxin, as seen with native inactivating BK channels. Inactivation arises from the N terminal of the ␤3 subunit. Removal of the ␤3 N terminal (33 amino acids) abolishes inactivation, whereas the addition of the ␤3 N terminal onto the ␤1 subunit confers inactivation. The ␤3 subunit shares with the ␤1 subunit an ability to shift the range of voltages over which channels are activated at a given Ca 2ϩ . Thus, the ␤-subunit family of BK channels regulates a number of critical aspects of BK channel phenotype, including inactivation and apparent Ca 2ϩ sensitivity.

show abstract

Section: Isolation Of Cdna Clonesmentioning

confidence: 99%

Section: Isolation Of Cdna Clonesmentioning

confidence: 99%

Molecular Basis for the Inactivation of Ca²⁺- and Voltage-Dependent BK Channels in Adrenal Chromaffin Cells and Rat Insulinoma Tumor Cells

Xia¹,

Ding²,

1999

View full text Add to dashboard Cite

show abstract

“…1;Meera et al, 1997;Wallner et al, 1996;Toro et al, 1998). The large C-terminus (containing about twice as many amino acids as S0-S6) has four hydrophobic domains (S7-S10), and Salkoff's group identified two molecular domains (S0-S8, "core" and S9-S10, "tail") that, when expressed together, were able to produce functional channels (Wei et al, 1994 A. D362/D367, M513 and the calcium bowl define sites that when mutated decrease the highaffinity Ca 2+ sensitivity of the BK channel. E374/E377 is a site that when mutated decreases the low affinity Ca 2+ and Mg 2+ sensitivity.…”

Section: Sensing Elementsmentioning

confidence: 99%

Large conductance Ca2+-activated K+ (BK) channel: Activation by Ca2+ and voltage

2006

View full text Add to dashboard Cite

Large conductance Ca 2+ -activated K + (BK) channels belong to the S4 superfamily of K + channels that include voltage-dependent K + (Kv) channels characterized by having six (S1-S6) transmembrane domains and a positively charged S4 domain. As Kv channels, BK channels contain a S4 domain, but they have an extra (S0) transmembrane domain that leads to an external NH 2 -terminus. The BK channel is activated by internal Ca 2+ , and using chimeric channels and mutagenesis, three distinct Ca 2+ -dependent regulatory mechanisms with different divalent cation selectivity have been identified in its large COOH-terminus. Two of these putative Ca 2+ -binding domains activate the BK channel when cytoplasmic Ca 2+ reaches micromolar concentrations, and a low Ca 2+ affinity mechanism may be involved in the physiological regulation by Mg 2+ . The presence in the BK channel of multiple Ca 2+ -binding sites explains the huge Ca 2+ concentration range (0.1 μM-100 μM) in which the divalent cation influences channel gating. BK channels are also voltage-dependent, and all the experimental evidence points toward the S4 domain as the domain in charge of sensing the voltage. Calcium can open BK channels when all the voltage sensors are in their resting configuration, and voltage is able to activate channels in the complete absence of Ca 2+ . Therefore, Ca 2+ and voltage act independently to enhance channel opening, and this behavior can be explained using a two-tiered allosteric gating mechanism.

show abstract

“…These channels are important in neurotransmitter release [145], motor control [146], alcohol sensitivity [147][148][149], blood pressure and the fine-tuning of hearing frequencies [150,151]. The STREX-encoded peptide lies in the Ca ++ -sensitivity domain at the COOH-terminal [30,152]. Inclusion of this exon confers higher voltage and Ca ++ sensitivity on the channel [24,[29][30][31]153], inhibition by PKA and oxidation [142,154], and sensitivity to glucocorticoids [143].…”

Section: Alternative Exons Regulated By Ca ++ Signalsmentioning

confidence: 99%

Control of alternative pre-mRNA splicing by Ca++ signals

Xie¹

2008

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanism

View full text Add to dashboard Cite

Alternative pre-mRNA splicing is a common way of gene expression regulation in metazoans. The selective use of specific exons can be modulated in response to various manipulations that alter Ca ++ signals, particularly in neurons. A number of splicing factors have also been found to be controlled by Ca ++ signals. Moreover, pre-mRNA elements have been identified that are essential and sufficient to mediate Ca ++ -regulated splicing, providing model systems for dissecting the involved molecular components. In neurons, this regulation likely contributes to the fine-tuning of neuronal properties.

show abstract

Calcium sensitivity of BK-type KCa channels determined by a separable domain

Cited by 237 publications

References 30 publications

Molecular Basis for the Inactivation of Ca²⁺- and Voltage-Dependent BK Channels in Adrenal Chromaffin Cells and Rat Insulinoma Tumor Cells

Molecular Basis for the Inactivation of Ca²⁺- and Voltage-Dependent BK Channels in Adrenal Chromaffin Cells and Rat Insulinoma Tumor Cells

Large conductance Ca2+-activated K+ (BK) channel: Activation by Ca2+ and voltage

Control of alternative pre-mRNA splicing by Ca++ signals

Contact Info

Product

Resources

About

Calcium sensitivity of BK-type KCa channels determined by a separable domain

Cited by 237 publications

References 30 publications

Molecular Basis for the Inactivation of Ca2+- and Voltage-Dependent BK Channels in Adrenal Chromaffin Cells and Rat Insulinoma Tumor Cells

Molecular Basis for the Inactivation of Ca2+- and Voltage-Dependent BK Channels in Adrenal Chromaffin Cells and Rat Insulinoma Tumor Cells

Large conductance Ca2+-activated K+ (BK) channel: Activation by Ca2+ and voltage

Control of alternative pre-mRNA splicing by Ca++ signals

Contact Info

Product

Resources

About

Molecular Basis for the Inactivation of Ca²⁺- and Voltage-Dependent BK Channels in Adrenal Chromaffin Cells and Rat Insulinoma Tumor Cells

Molecular Basis for the Inactivation of Ca²⁺- and Voltage-Dependent BK Channels in Adrenal Chromaffin Cells and Rat Insulinoma Tumor Cells