In this review, we give a state-of-the-art account of uterine contractility, focussing on excitation-contraction (electro-mechanical) coupling (ECC). This will show how electrophysiological data and intracellular calcium measurements can be related to more modern techniques such as confocal microscopy and molecular biology, to advance our understanding of mechanical output and its modulation in the smooth muscle of the uterus, the myometrium. This new knowledge and understanding, for example concerning the role of the sarcoplasmic reticulum (SR), or stretch-activated K channels, when linked to biochemical and molecular pathways, provides a clearer and better informed basis for the development of new drugs and targets. These are urgently needed to combat dysfunctions in excitation-contraction coupling that are clinically challenging, such as preterm labour, slow to progress labours and post-partum haemorrhage. It remains the case that scientific progress still needs to be made in areas such as pacemaking and understanding interactions between the uterine environment and ion channel activity.
SUMMARYBecause of the reported presence of a Na+-Mg2' exchanger in guinea-pig but not in ferret myocardium, the Mg2+ extrusion mechanism in guinea-pig myocardium has been reinvestigated using Mg2+-and Na+-selective microelectrodes and the fluorochromes mag-fura- In vitro calibration of mag-fura-2 and -5 using the ratio method gave values for Kd (experimentally determined dissociation constant) of 22 2 + 2-7 (mean + S.D., n = 7) and 25-7+ 1 3 (n = 4) mmol/l respectively. Mag-fura-2 reacted to physiological concentrations of Ca2+ and mag-fura-5 to changes in pH. In isolated myocytes, Na+ removal gave an apparent increase of [Mg2+], with mag-fura-2 but not with mag-fura-5. However, when the pH, was altered with NH4Cl mag-fura-5 showed an apparent decrease in [Mg2+]i on application and an apparent increase on removal, with a time course similar to the pH, changes. It is concluded that Mg2+ extrusion in guinea-pig myocardium is not via a Na+-Mg2+ exchanger. The use of mag-fura-2 and -5 are limited in their application because of Ca2+ and H+ sensitivity respectively.
SUMMARY1. A method is described for determining the space constant A of heart muscle strips using a sucrose gap technique.2. The average value of A for frog atrial trabeculae was found to be nearly 700,um. This value is nearly twice the length of the test gap (400 /sm). Near the resting potential, the voltage non-uniformity should be about 10%. This was confirmed experimentally by comparing the membrane voltages recorded across the current-passing and voltagerecording sucrose gaps.3. The non-uniformity during large depolarizations was calculated using a computer model. This model includes the inward-going rectification displayed by i~K and the delayed rectification that occurs following depolarizations beyond -40 mV. A single component of delayed rectification was included.4. It is shown that even very large non-uniformities have relatively small effects on the shape of the activation curve and on the time course of onset or decay of current.5. It is concluded that the fast component of current decay described in a previous paper (Brown, Clark & Noble, 1976b) is not attributable to a non-uniformity artifact.
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