Role of K+ channels in maintaining the synchrony of spontaneous Ca2+ transients in the mural cells of rat rectal submucosal arterioles
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Mural cells in precapillary arterioles (PCAs) generate spontaneous Ca2+ transients primarily arising from the periodic release of Ca2+ from sarcoendoplasmic reticulum (SR/ER). The Ca2+ release induces Ca2+-activated chloride channel (CaCC)-dependent depolarisations that spread to neighbouring mural cells to develop the synchrony of their Ca2+ transients. Here, we explored the roles of K+ channels in maintaining the synchrony of spontaneous Ca2+ transients. Intracellular Ca2+ dynamics in mural cells were visualised by Cal-520 fluorescence Ca2+ imaging in the submucosal PCAs of rat rectum. Increasing extracellular K+ concentration ([K+]o) from 5.9 to 29.7 mM converted synchronous spontaneous Ca2+ transients into asynchronous, high-frequency Ca2+ transients. Similarly, the blockade of inward rectifier K+ (Kir) channels with Ba2+ (50 μM) or Kv7 voltage-dependent K+ (Kv7) channels with XE 991 (10 μM) disrupted the synchrony of spontaneous Ca2+ transients, while the blockers for large-, intermediate- or small-conductance Ca2+-activated K+ channels had no effect. Kir2.1 immunoreactivity was detected in the arteriolar endothelium but not mural cells. In the PCAs that had been pretreated with XE 991 or Ba2+, nifedipine (1 μM) attenuated the asynchronous Ca2+ transients but failed to restore their synchrony. In contrast, levcromakalim, an ATP-sensitive K+ channel opener, restored the synchronous Ca2+ transients. Thus, constitutively active Kv7 and Kir channels appear to be involved in maintaining the relatively hyperpolarised membrane of mural cells. The hyperpolarised membrane prevents depolarisation-induced ‘premature’ Ca2+ transients to ensure sufficient SR/ER Ca2+ refilling that is required for regenerative Ca2+ release resulting in synchronous Ca2+ transients amongst the mural cells.
KeywordsMicrovasculature Mural cells Spontaneous Ca2+ transient Intercellular synchrony K+ channels
Area under curve
Ca2+-activated Cl− channel
Cyclic guanosine monophosphate
Endothelial nitric oxide synthase
- IK channel
Intermediate-conductance Ca2+-activated K+ channel
Extracellular K+ concentration
- KATP channel
ATP-sensitive K+ channel
- Kir channel
Inward rectifier K+ channel
- Kv7 channel
Kv7 voltage-dependent K+ channel
L-type voltage-dependent Ca2+ channel
Physiological salt solution
- SK channel
Small-conductance Ca2+-activated K+ channel
T-type voltage-dependent Ca2+ channel
The authors wish to thank Dr. Richard Lang (Monash University) for his critical reading of the manuscript and also Dr. Hiromichi Takano (Nagoya City University) for his advice on experiments.
The present study was partly supported by Grant-in-Aid for Young Scientists (B) (No. 16K19361) from Japan Society for Promotion of the Science (JSPS) to R.M., Grant-in-Aid for Scientific Research (C) (No. 17K11187) from JSPS to H.H. and a grant-in-aid of the 24th General Assembly of the Japanese Association of Medical Sciences to R.M.
Compliance with ethical standards
Conflict of interest
There is no conflict of interest.
The experimental protocols in the present study were approved by the animal experimentation ethics committee at Nagoya City University Graduate School of Medical Sciences.
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