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Updated: Jul 14, 2026
Functional Assessment of Intestinal Tight Junction Barrier and Ion Permeability in Native Tissue by Ussing Chamber Technique
Published on: May 26, 2021
Ca2+ channel currents and contraction in CaVbeta3-deficient ileum smooth muscle from mouse
Brigitte Held1, Volodymyr Tsvilovskyy, Marcel Meissner
1Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Medizinische Fakultät, Universität des Saarlandes, D-66421 Homburg, Germany. brigitte.held@uks.eu
Abstract:
Voltage activated L-type Ca(2+) channels are the principal Ca(2+) channels in intestinal smooth muscle cells. They comprise the ion conducting Ca(V)1 pore and the ancillary subunits alpha(2)delta and beta. Of the four Ca(V)beta subunits Ca(V)beta(3) is assumed to be the relevant Ca(V)beta protein in smooth muscle. In protein lysates isolated from mouse ileum longitudinal smooth muscle we could identify the Ca(V)1.2, Ca(V)alpha(2), Ca(V)beta(2) and Ca(V)beta(3) proteins, but not the Ca(V)beta(1) and Ca(V)beta(4) proteins. Protein levels of Ca(V)1.2, Ca(V)alpha(2) and Ca(V)beta(2) are not altered in ileum smooth muscle obtained from Ca(V)beta(3)-deficient mice indicating that there is no compensatory increase of the expression of these channel proteins. Neither the Ca(V)beta(2) nor the other Ca(V)beta proteins appear to substitute for the lacking Ca(V)beta(3). L-type Ca(2+) channel properties including current density, inactivation kinetics as well as Cd(2+)- and dihydropyridine sensitivity were identical in cells of both genotypes suggesting that they do not require the presence of a Ca(V)beta(3) protein. However, a key hallmark of the Ca(V)beta modulation of Ca(2+) current, the hyperpolarisation of channel activation is slightly but significantly reduced by 4 mV. In addition to L-type Ca(2+) currents T-type Ca(2+) currents could be recorded in the murine ileum smooth muscle cells, but T-type currents were not affected by the lack of Ca(V)beta(3). Both proteins, Ca(V)beta(2) and Ca(V)beta(3) are localized near the plasma membrane and the localization of Ca(V)beta(2) is not altered in Ca(V)beta(3) deficient cells. Spontaneous contractions and potassium and carbachol induced contractions are not significantly different between ileum longitudinal smooth muscle strips from mice of both genotypes. In summary the data show that in ileum smooth muscle cells, Ca(V)beta(3) has only subtle effects on L-type Ca(2+) currents, appears not to be required for spontaneous and potassium induced contraction but might have a function beyond being a Ca(2+) channel subunit.
Insights
Calcium channel subunit Ca(V)beta(3) has subtle effects on L-type Ca(2+) currents in intestinal smooth muscle. Its absence does not impact channel function or muscle contractions, suggesting roles beyond ion channel modulation.
Area of Science:
- Molecular and Cellular Physiology
- Ion Channel Biology
- Smooth Muscle Physiology
Background:
- Voltage-activated L-type Ca(2+) channels are crucial for intestinal smooth muscle cell function.
- These channels comprise Ca(V)1 pore-forming subunits and ancillary beta subunits, with Ca(V)beta(3) presumed to be key in smooth muscle.
Purpose of the Study:
- To investigate the role of the Ca(V)beta(3) subunit in intestinal smooth muscle L-type Ca(2+) channels.
- To determine if Ca(V)beta(3) is essential for channel function, localization, and smooth muscle contraction.
Main Methods:
- Analysis of protein expression in ileum smooth muscle from wild-type and Ca(V)beta(3)-deficient mice.
- Electrophysiological recordings (L-type and T-type currents) and assessment of channel properties (current density, kinetics, drug sensitivity).
- Evaluation of spontaneous, potassium-, and carbachol-induced smooth muscle contractions.
Main Results:
- Ca(V)beta(3) deficiency did not alter the expression or localization of other key channel subunits (Ca(V)1.2, Ca(V)alpha(2), Ca(V)beta(2)).
- L-type Ca(2+) channel properties were largely unaffected, except for a minor reduction in activation hyperpolarization, indicating Ca(V)beta(3) is not essential for core channel function.
- Absence of Ca(V)beta(3) did not affect T-type currents or the contractile responses of intestinal smooth muscle strips.
Conclusions:
- Ca(V)beta(3) plays a subtle modulatory role in L-type Ca(2+) currents in intestinal smooth muscle.
- Ca(V)beta(3) is not required for the primary function of these channels or for smooth muscle contractility.
- The Ca(V)beta(3) subunit may possess functions independent of its role as a Ca(2+) channel auxiliary subunit.
