Journal article
Permissive Modulation of Sphingosine-1-Phosphate-Enhanced Intracellular Calcium on BKCa Channel of Chromaffin Cells
International journal of molecular sciences, Vol.22(4), p.2175
02/01/2021
DOI: 10.3390/ijms22042175
PMID: 33671654
Abstract
Sphingosine-1-phosphate (S1P), is a signaling sphingolipid which acts as a bioactive lipid mediator. We assessed whether S1P had multiplex effects in regulating the large-conductance Ca
2+
-activated K
+
channel (BK
Ca
) in catecholamine-secreting chromaffin cells. Using multiple patch-clamp modes, Ca
2+
imaging, and computational modeling, we evaluated the effects of S1P on the Ca
2+
-activated K
+
currents (
I
K(Ca)
) in bovine adrenal chromaffin cells and in a pheochromocytoma cell line (PC12). In outside-out patches, the open probability of BK
Ca
channel was reduced with a mean-closed time increment, but without a conductance change in response to a low-concentration S1P (1 µM). The intracellular Ca
2+
concentration (Ca
i
) was elevated in response to a high-dose (10 µM) but not low-dose of S1P. The single-channel activity of BK
Ca
was also enhanced by S1P (10 µM) in the cell-attached recording of chromaffin cells. In the whole-cell voltage-clamp, a low-dose S1P (1 µM) suppressed
I
K(Ca)
, whereas a high-dose S1P (10 µM) produced a biphasic response in the amplitude of
I
K(Ca)
, i.e., an initial decrease followed by a sustained increase. The S1P-induced
I
K(Ca)
enhancement was abolished by BAPTA. Current-clamp studies showed that S1P (1 µM) increased the action potential (AP) firing. Simulation data revealed that the decreased BK
Ca
conductance leads to increased AP firings in a modeling chromaffin cell. Over a similar dosage range, S1P (1 µM) inhibited
I
K(Ca)
and the permissive role of S1P on the BK
Ca
activity was also effectively observed in the PC12 cell system. The S1P-mediated
I
K(Ca)
stimulation may result from the elevated Ca
i
, whereas the inhibition of BK
Ca
activity by S1P appears to be direct. By the differentiated tailoring BK
Ca
channel function, S1P can modulate stimulus-secretion coupling in chromaffin cells.
Details
- Title: Subtitle
- Permissive Modulation of Sphingosine-1-Phosphate-Enhanced Intracellular Calcium on BKCa Channel of Chromaffin Cells
- Creators
- Adonis Z Wu - Krannert Institute of Cardiology and Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USATzu-Lun Ohn - Institute of Zoology, National Taiwan University, Taipei 106319, TaiwanRen-Jay Shei - Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine and Gregory Fleming James Cystic Fibrosis Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USAHuei-Fang Wu - Neuroscience Program of Academia Sinica, Academia Sinica, Taipei 115201, TaiwanYong-Cyuan Chen - Institute of Zoology, National Taiwan University, Taipei 106319, TaiwanHsiang-Chun Lee - Division of Cardiology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807378, TaiwanDao-Fu Dai - Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung 807378, TaiwanSheng-Nan Wu - Department of Physiology, National Cheng-Kung University Medical College, Tainan 701401, Taiwan
- Resource Type
- Journal article
- Publication Details
- International journal of molecular sciences, Vol.22(4), p.2175
- DOI
- 10.3390/ijms22042175
- PMID
- 33671654
- NLM abbreviation
- Int J Mol Sci
- ISSN
- 1422-0067
- eISSN
- 1422-0067
- Publisher
- MDPI
- Grant note
- DOI: 10.13039/501100001868, name: National Science Council, award: NSC 94-2627-M-002-003, NSC-94-2320B-006-019; DOI: 10.13039/501100004694, name: Kaohsiung Medical University, award: 105KMUOR08, KMUH109-9R11; DOI: 10.13039/501100001869, name: Academia Sinica, award: AS-CFII-110-101; DOI: 10.13039/100000002, name: National Institutes of Health, award: HL145138-02; DOI: 10.13039/100010506, name: Indiana University Health, award: KIC2019FA
- Language
- English
- Date published
- 02/01/2021
- Academic Unit
- Pathology; Iowa Neuroscience Institute; Radiation Oncology
- Record Identifier
- 9984070693302771
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