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15:28
Mutagenesis and Functional Analysis of Ion Channels Heterologously Expressed in Mammalian Cells
Published on: October 2, 2010
Gating and ionic currents reveal how the BKCa channel's Ca2+ sensitivity is enhanced by its beta1 subunit
1Molecular Cardiology Research Institute, New England Medical Center, Boston, MA 02111, USA.
The Journal of General Physiology
|September 28, 2005
Summary
The beta1 subunit enhances large-conductance Ca(2+)-activated K(+) (BK(Ca)) channel Ca(2+) sensitivity in smooth muscle by stabilizing voltage sensors. This mechanism improves smooth muscle tone regulation by altering the channel
Area of Science:
- Ion channel physiology
- Molecular biophysics
- Smooth muscle biology
Background:
- Large-conductance Ca(2+)-activated K(+) (BK(Ca)) channels are crucial for regulating smooth muscle tone.
- Tissue-specific auxiliary beta subunits modulate BK(Ca) channel function.
- The beta1 subunit, predominantly in smooth muscle, significantly increases BK(Ca) channel Ca(2+) sensitivity.
Purpose of the Study:
- To elucidate the molecular mechanism by which the beta1 subunit enhances BK(Ca) channel Ca(2+) sensitivity.
- To investigate the effects of beta1 on voltage sensing and Ca(2+) binding within the BK(Ca) channel.
Main Methods:
- Gating current recordings
- Macroscopic ionic current recordings
- Unitary ionic current recordings at very low open probabilities
Main Results:
- Beta1 subunit stabilizes voltage sensor activation at more negative voltages.
- Beta1 subunit reduces the contribution of voltage sensor activation to channel opening.
- Beta1 subunit decreases the work required for Ca(2+) binding to open the channel.
- Beta1 subunit may decrease the true Ca(2+) affinity of the closed channel.
Conclusions:
- Beta1 subunit enhances BK(Ca) channel Ca(2+) sensitivity primarily by altering voltage sensor kinetics.
- These alterations in voltage sensing reduce the energetic barrier for channel opening, thereby increasing apparent Ca(2+) sensitivity.
- The findings provide a mechanistic basis for beta1 subunit's role in smooth muscle function.
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