Properties of synchronous spontaneous Ca2+ transients in the mural cells of rat rectal arterioles

Abstract

Synchrony of spontaneous Ca2+ transients among venular mural cells (smooth muscle cells and pericytes) in visceral organs relies on the intercellular spread of L-type voltage-dependent Ca2+ channel (LVDCC)-dependent depolarisations. However, the mechanisms underlying the synchrony of spontaneous Ca2+ transients between arteriolar mural cells are less understood. The spontaneous intracellular Ca2+ dynamics of arteriolar mural cells in the rat rectal submucosa were visualised by Cal-520 Ca2+ imaging to analyse their synchrony. The mural cells in fine arterioles that had a rounded cell body with several extended processes developed spontaneous ‘synchronous’ Ca2+ transients arising from Ca2+ released from sarcoendoplasmic reticulum Ca2+ stores. Gap junction blockers (3 μM carbenoxolone, 10 μM 18β-glycyrrhetinic acid), a Ca2+-activated Cl channel (CaCC) blocker (100 μM 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid) or lowering extracellular Cl concentration (from 134.4 to 12.4 mM) disrupted the synchrony of Ca2+ transients between arteriolar mural cells. Blockers of T-type voltage-dependent Ca2+ channels (TVDCCs, 1 μM mibefradil or ML218) or LVDCCs (1 μM nifedipine) reduced the Ca2+ transient frequency or their area under curve (AUC), respectively. However, neither TVDCC nor LVDCC blockers disrupted the synchrony of Ca2+ transients among arteriolar mural cells. This is in contrast with rectal venules in which nifedipine disrupted the synchrony of spontaneous Ca2+ transients. Thus, spontaneous transient depolarisations arising from the opening of CaCCs may effectively spread to neighbouring arteriolar mural cells via gap junctions to maintain the Ca2+ transient synchrony. Activation of TVDCCs appears to accelerate spontaneous Ca2+ transients, while LVDCCs predominantly contribute to the duration of Ca2+ transients.

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Abbreviations

α-SMA:

α-Smooth muscle actin

AUC:

Area under curve

CaCC:

Ca2+-activated Cl channel

LVDCC:

L-type voltage-dependent Ca2+ channel

GI:

Gastrointestinal

NG2:

NG2 chondroitin sulphate proteoglycan

PSS:

Physiological salt solution

TVDCC:

T-type voltage-dependent Ca2+ channel

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Acknowledgements

The authors wish to thank Dr. Richard Lang (Monash University) for critical reading of the manuscript. The present study was partly supported by Grant-in-Aid for Young Scientists (B) (No. 26860521 and No. 16K19361) from Japan Society for Promotion of the Science (JSPS) to R.M., Grant-in-Aid for Challenging Exploratory Research (No. 26670705) from JSPS to H.H. and Grant-in-Aid from The Hori Sciences and Arts Foundation to R.M.

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Correspondence to Retsu Mitsui.

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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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Mitsui, R., Hashitani, H. Properties of synchronous spontaneous Ca2+ transients in the mural cells of rat rectal arterioles. Pflugers Arch - Eur J Physiol 469, 1189–1202 (2017). https://doi.org/10.1007/s00424-017-1978-y

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Keywords

  • Blood vessel
  • Microvasculature
  • Smooth muscles
  • Ca2+ signalling
  • Intestine