Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCA368

Poster Communications

How Does Extracellular Acidification Increase Mouse Uterine Contractions?
How much do we know?

A. M. Almohanna1,2, S. Wray1

1. University of Liverpool, Liverpool, United Kingdom. 2. Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.


Adequate uterine contraction is crucial to safe delivery of the foetus. Acidity can play an important role in affecting myometrial contraction but the effects, especially concerning external acidification, are unclear. We have found that extracellular acidification (pHo) consistently increases the contractility of mouse myometrium. Here we are investigating the possible mechanism/s behind the stimulatory effect of acidic pHo. In uterine tissue from pregnant mouse, a decrease of pHo stimulated contraction, particularly by increasing their amplitude and frequency. These data are consistent with the large increases in force found in non-pregnant guinea-pig myometrium (Naderali and Wray, 1999), and an increased frequency (but not amplitude) in pregnant human myometrium (Pierce et al., 2003). Ion channels sensitive to external acid and conducting inward current (ASICs) have been reported in nervous tissues. Although our western blot data showed expression of ASICs in the mouse myometrium, inhibition of the ASICs by Amiloride did not affect the stimulatory effect of the acidic pHo. These data suggest either that the ASICs are non-functional or that they were not stimulated by an external pH of 6.9. As the simultaneous measurement of the pHi showed a drop in the pH inside the cell in response to the change in the pHo, these data showed the changes of force more closely followed the change of external pH than intracellular pH. Membrane depolarization opens the L-type calcium channels (LVCC) resulting in calcium influx and initiation of uterine contractions. Blocking LVCC decreased the force of contraction but still pHo increased the force. This suggests that external acidification is acting on another type of channels that assists calcium entry. The relation between extracellular acidification and cell membrane depolarization was tested. Extracellular acidification, under high KCl, caused initial increase in the force. These findings also suggest other depolarizing channels which are activated by extracellular acidification and allow more calcium influx. P2X receptors are cation-selective channels, located on the plasma membrane and they are mainly gated by extracellular ATP, and mediate the influx of extracellular cations (Ca2+ and Na+) into the cell, which subsequently depolarize the membrane and open voltage-gated CCs. However, P2X7 purinoceptors blockade by hydrochloride hydrate didn't affect the stimulatory effect of acidic pHo. We therefore conclude that external acidification within the physiological range, increases force by a mechanism that is not via ASICs, purinoceptors or directly on L-type Ca channels, Work is ongoing to test other possible mechanisms.

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