α1-Adrenergic stimulation increases the Vmax of isolated myocardial papillary muscles

1991 ◽  
Vol 69 (12) ◽  
pp. 1804-1809 ◽  
Author(s):  
Kai Li ◽  
Jean L. Rouleau

α-Adrenergic agonists have been shown to increase the tension developed by myocardial muscle. However, their effects on the maximum velocity of unloaded muscle shortening (Vmax) have not been rigorously examined. In this study, the contractile effects of the α-adrenergic agonist phenylephrine were examined in the presence of propranolol in papillary muscles of two species, the dog and the rabbit. In rabbit papillary muscles studied at physiological calcium concentrations (1.25 mM), phenylephrine increased all indices of contractility (Vmax, tension, and maximum rate of tension developed (dT/dt)) starting at 10−8 M. The percent increase in Vmax (121 ± 8%) was less than that of tension (188 ± 20%, p < 0.05) and dT/dt (262 ± 35%, p < 0.01). These findings occurred at both 29 and 35 °C and were inhibited by adding 10−5 M prazosin. Increasing extracellular calcium concentration from 1.25 to 15 mM caused changes in twitch configuration that were significantly different from those of phenylephrine. Calcium increased all indices of contractility more than did phenylephrine. This was particularly true for dT/dt (502 ± 82 vs. 262 ± 35% for phenylephrine, p < 0.01). Nonetheless, the ratio of increase in tension to increase in Vmax under both experimental conditions was similar (the increase in Vmax was 64% of that of tension with phenylephrine and 69% with increased calcium). At 1.25 mM calcium, the increase in contractility caused by phenylephrine was much smaller in dog myocardium as compared with rabbit myocardium. Rather, the effects of phenylephrine on dog myocardium studied at 1.25 mM calcium resembled that of rabbit myocardium studied at 15 mM calcium. We conclude that (i) α1-adrenergic receptor stimulation increases all indices of contractility at a similar threshold concentration but increases Vmax relatively less; (ii) despite markedly different effects on the intensity of the cytosolic calcium transient and twitch configuration characteristics, the increase in Vmax relative to tension caused by phenylephrine is similar to that caused by increasing extracellular calcium concentration; (iii) species differences in myocardial contractile response to α1-adrenergic stimulation exist, and that some of these differences can be abolished by altering extracellular calcium.Key words: α1-adrenergic, Vmax, contractility, calcium.

Endocrine ◽  
2021 ◽  
Vol 71 (3) ◽  
pp. 611-617
Author(s):  
Judit Tőke ◽  
Gábor Czirják ◽  
Péter Enyedi ◽  
Miklós Tóth

AbstractThe calcium-sensing receptor (CaSR) provides the major mechanism for the detection of extracellular calcium concentration in several cell types, via the induction of G-protein-coupled signalling. Accordingly, CaSR plays a pivotal role in calcium homeostasis, and the CaSR gene defects are related to diseases characterized by serum calcium level changes. Activating mutations of the CaSR gene cause enhanced sensitivity to extracellular calcium concentration resulting in autosomal dominant hypocalcemia or Bartter-syndrome type V. Inactivating CaSR gene mutations lead to resistance to extracellular calcium. In these cases, familial hypocalciuric hypercalcaemia (FHH1) or neonatal severe hyperparathyroidism (NSHPT) can develop. FHH2 and FHH3 are associated with mutations of genes of partner proteins of calcium signal transduction. The common polymorphisms of the CaSR gene have been reported not to affect the calcium homeostasis itself; however, they may be associated with the increased risk of malignancies.


1993 ◽  
Vol 264 (6) ◽  
pp. E863-E867 ◽  
Author(s):  
E. Gorczynska ◽  
D. J. Handelsman

The prompt rise in cytosolic calcium induced by follicle-stimulating hormone (FSH) in rat Sertoli cells suggests a role for calcium in FSH signal transduction. To evaluate the requirement for sodium in transmembrane calcium fluxes in Sertoli cells, we measured intracellular calcium concentration under sodium-free conditions and during stimulation by monensin and veratridine, used to elevate cytosolic sodium. Cytosolic calcium levels were measured by dual-wavelength spectrofluorimetry using freshly isolated cells loaded with fura-2 acetoxymethyl ester. Whereas, removal of extracellular sodium lowered cytosolic calcium in unstimulated cells from 89 +/- 4 to 75 +/- 8 nM, treatment with monensin and veratridine increased cytosolic calcium to 142 +/- 19 and 126 +/- 13 nM, respectively. Without extracellular calcium, monensin still produced 47% of the rise in cytosolic calcium observed in the presence of extracellular calcium, indicating approximately equal contributions of calcium from intracellular and extracellular sources. Blockade of voltage-sensitive or/and voltage-insensitive calcium channels by verapamil and ruthenium red was unable to completely prevent the monensin-induced elevation of cytosolic calcium. In addition tetrodotoxin failed to block the FSH-induced rise in cytosolic calcium. These observations, together with the considerable reduction in monensin-induced rise in cytosolic calcium under extracellular sodium-free condition, support the hypothesis that sodium-calcium exchange rather than the specific calcium or sodium channels regulate basal and monensin-induced transmembrane sodium and calcium fluxes in Sertoli cells.


1975 ◽  
Vol 228 (2) ◽  
pp. 628-632 ◽  
Author(s):  
NL Stephens ◽  
EA Kroeger ◽  
U Kromer

In multi-unit tracheal smooth muscle (TSM), quick stretches applied at a velocity of 5 times the measured maximum velocity of isotonic shortening of the muscle, of a magnitude 3 times the measured extension of the series-elastic component when the muscle contracts maximally, and at optimal muscle length (L-o) were unable to elicit any myogenic response (MR). Experimental conditions such as hypoxia (P-O2 smaller than 60 mmHg) and acidosis (pH equals 6.8) or the presence of Ba2+ (2 mM), acetylcholine (10-6 M), or high (K+)-o (59 mM) were also unable to elicit the MR. However, tetraethylammonium chloride (TEA, 0.4-67 mM) produces 1) spontaneous phasic contractions and 2) a MR to quick stretch. The ionic basis for these changes was then investigated by studying the Ca and Mg dependence of the response to TEA. The dose-response relationship to TEA was shifted to the left by decreasing external Mg2+ from 2.5 to 0.5 mM. The ability of TSM to produce a MR was absolutely dependent on external Ca, but the threshold concentration required shifted from 2.5 times 10-5 M at normal external Mg (2.5 mM) to 5 times 10-4 M at the reduced external Mg (0.5 mM). The effects of TEA on spontaneity and the MR were abolished by D-600. These results suggest that 1) TEA functionally converts multiunit smooth muscle into a single unit one and leads to the development of a MR and 2) the MR results from a depolarization-activated mobilization of Ca and is inhibited by ionic conditions known to increase membrane permeability.


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