Regulation of an amiloride‐sensitive Na+‐permeable channel by a β2‐adrenergic agonist, cytosolic Ca2+ and Cl− in fetal rat alveolar epithelium
Y Marunaka, N Niisato, H O'Brodovich… - The Journal of …, 1999 - Wiley Online Library
Y Marunaka, N Niisato, H O'Brodovich, DC Eaton
The Journal of Physiology, 1999•Wiley Online Library1 In cell‐attached patches formed on the apical membrane of fetal alveolar epithelium,
terbutaline (a specific β2‐adrenergic agonist) increased the open probability (Po) of an
amiloride‐sensitive Na+‐permeable non‐selective cation (NSC) channel (control,
0.03±0.04; terbutaline, 0.62±0.18; n= 8, P< 0.00001) by increasing the mean open time 100‐
fold without any significant change in the mean closed time and without any change in the
single channel conductance (control, 27.8±2.3 pS; terbutaline, 28.2±2.1 pS; n= 8). 2 The Po …
terbutaline (a specific β2‐adrenergic agonist) increased the open probability (Po) of an
amiloride‐sensitive Na+‐permeable non‐selective cation (NSC) channel (control,
0.03±0.04; terbutaline, 0.62±0.18; n= 8, P< 0.00001) by increasing the mean open time 100‐
fold without any significant change in the mean closed time and without any change in the
single channel conductance (control, 27.8±2.3 pS; terbutaline, 28.2±2.1 pS; n= 8). 2 The Po …
- 1In cell‐attached patches formed on the apical membrane of fetal alveolar epithelium, terbutaline (a specific β2‐adrenergic agonist) increased the open probability (Po) of an amiloride‐sensitive Na+‐permeable non‐selective cation (NSC) channel (control, 0.03 ± 0.04; terbutaline, 0.62 ± 0.18; n= 8, P < 0.00001) by increasing the mean open time 100‐fold without any significant change in the mean closed time and without any change in the single channel conductance (control, 27.8 ± 2.3 pS; terbutaline, 28.2 ± 2.1 pS; n= 8).
- 2The Po of the unstimulated channel increased when the apical membrane was depolarized due to a decrease in the closing rate and an increase in the opening rate, while the Po of the terbutaline‐stimulated channel did not depend on the membrane potential.
- 3Increased cytosolic [Ca2+] also increased the Po of the channel in a manner consistent with one Ca2+‐binding site on the cytosolic surface of the channel. Terbutaline increased the sensitivity of the channel to cytosolic Ca2+ by shifting the concentration of cytosolic Ca2+ ([Ca2+]c) required for half‐maximal activation to a lower [Ca2+]c value, leading to an increase in Po.
- 4An increase in the cytosolic Cl− concentration ([Cl−]c) decreased the Po of the channel consistent with two Cl−‐binding sites by increasing the closing rate without any significant change in the opening rate. Terbutaline increased Po by reducing the effect of cytosolic Cl− to promote channel closing.
- 5Taken together, these observations indicate that terbutaline activates a Ca2+‐activated, Cl−‐inhibitable, amiloride‐sensitive, Na+‐permeable NSC channel in fetal rat alveolar epithelium in two ways: first, through an increase in Ca2+ sensitivity, and second, through a reduction in the effect of cytosolic Cl− to promote channel closing.
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