EFFECTS OF IONS ON VASCULAR SMOOTH MUSCLE 



I] 57 



showed the importance of penetrability of the ac- 

 companying anion, and improved the relation of E„, 

 to log K„ to yield a slope of 45 mv. This is still lower, 

 however, than the ideal 58 mv which one would 

 expect. 



Holman (116) found more evidence to relate E„, 

 and tension. She reported that raising Na„ to two or 

 three times the normal level first increased tension and 

 spike rate while reducing E m . Later, as exposure was 

 prolonged, the spikes disappeared although tension 

 remained high and E„, low. These observations again 

 argue for dissociation of spikes and tension, but later, 

 Holman (118) took the position that spike frequency 

 was an important factor in the development of ten- 

 sion and Axelsson (5) sustained this view. 



The question of whether or not tension changes 

 and electrical spikes are interdependent is of particu- 

 lar importance to our problem, since vascular tissue, 

 so far as it has been studied, shows no spike activity 

 whatever. Accordingly, tissues such as taenia coli are 

 relevant only insofar as their tension may correlate 

 with electrical activity other than that of a train of 

 action potentials constituting the spike activity. Burn- 

 stock's recent study and argument is thus particularly 

 important (24). He noted that smooth muscle of 

 guinea pig taenia coli is relaxed by epinephrine and 

 that this is associated with a rise in E m and decrease 

 of spike activity. The smooth muscle of the muscularis 

 mucosa of the dog, by contrast, is contracted by 

 epinephrine and in this case the epinephrine effect is 

 associated with a fall in E„, and an increase in spike 

 activity. It would therefore appear that at least for 

 these types of visceral muscle both the membrane 

 potential and the spike activity are correlated with 

 tension. Under certain circumstances it is possible to 

 dissociate the spike activity from the tension and the 

 membrane potential alone then remains inversely 

 correlated. 



A similar situation arises in connection with studies 

 of the uterus. The observation of Woodbury & Mc- 

 Intyre (212) that oxytocin, which contracts the 

 pregnant uterus, reverses the membrane potentials of 

 the single muscle cell is quite relevant for it again 

 relates membrane potential to activity. On the other 

 hand, the claim (43) that tension of the uterus strip is 

 only correlated with spike activity suggests that this 

 tissue is not analogous to vascular smooth muscle. 



Electrical studies of vascular smooth muscle were 

 almost nonexistent until very recently. Bozler (17) 

 considered this type of muscle to be distinctive in 

 being "multi-unit" unlike many other types which 

 behave like single units. Recent detailed and elegant 



studies by Burnstock & Prosser (25) and Prosser et al. 

 (161) have placed this on a firmer footing. Vascular 

 smooth muscle is here shown to consist of widely sepa- 

 rated cells and its extracellular space calculated from 

 electron microscopy is about 40 per cent of the total 

 (see table 4). This contrasts strikingly with the other 

 types of smooth muscle in which the extracellular 

 space is estimated at less than 20 per cent. Vascular 

 smooth muscle shows no conducted electrical activity 

 and no spikes. Our theoretical discussion must reckon 

 with these distinctive features. 2 



ROLE OF CALCIUM AND MAGNESIUM IN 

 VASCULAR SMOOTH MUSCLE TENSION 



Calcium 



There is too little information concerning the de- 

 tailed effects of calcium and magnesium on vascular 

 tissue to permit any elaborate discussion. What little 

 evidence we do have is fortunately consistent. The 

 older literature has been reviewed by Evans (60). A 

 much larger literature deals with the general direct 

 involvement of calcium in the actomyosin system (51) 

 and in the metabolic cycle of cells (141). We shall 

 not develop this broad field of physiological chemistry, 

 which would lead us far from our immediate subject, 

 but we must note that calcium ions are evidently 

 necessary for the contractile machinery to work. 



The physiological implications of this have been 

 demonstrated by Heilbrunn & Wiercinski (1 10). They 

 showed that Ca in high dilution injected directly into 

 the single skeletal muscle fiber caused an immediate 

 and pronounced shortening. This effect is not shared 

 by any other ion normally present in any quantity 

 in muscle, but it is also produced by Ba. These au- 

 thors, like others since (142), support the view that 

 Ca links the ionic processes at the membrane to the 

 contractile mechanism. This point obviously has as 

 much importance for contraction and tonus in vascu- 

 lar as in any other muscle tissue. 



In studies of intestinal segments there seems to be 

 general agreement that the addition of Ca to the 

 medium increases tone (189, 208). More important 

 to our thesis is the demonstration that withdrawal of 



2 Recent successful impalement of single smooth muscle cells 

 in turtle aorta and inferior vena cava segments has shown 

 specialized types of action potential in association with tension 

 changes. (Roddie, I. C. and S. Kirk. Transmembrane action 

 potentials from smooth muscle in turtle arteries and veins. 

 Science 134: 736, 1961.) 



