scholarly journals Calcium and muscle contraction: the triumph and tragedy of Lewis Victor Heilbrunn

2019 ◽  
Vol 43 (4) ◽  
pp. 476-485
Author(s):  
Jack A. Rall
Keyword(s):  
Muscle Contraction ◽  
Intracellular Calcium ◽  
Sea Urchin ◽  
Convincing Evidence ◽  
Thought Process ◽  
Origin And Evolution ◽  
Cell Calcium ◽  
Scientific Philosophy ◽  
Muscle Contract

Lewis Victor Heilbrunn has been called the pioneer of Ca2+ as an intracellular regulator (Campbell AK. Cell Calcium 7: 287–296, 1986; Campbell AK. Intracellular Calcium, 2015). In 1947, he was the first to provide convincing evidence that Ca2+ triggered muscle contraction (Heilbrunn LV, Wiercinski FJ. J Cell Comp Physiol 29: 15–32, 1947). Yet his work was met mostly with silence and neglect. One wonders why. Heilbrunn was a general physiologist who believed in the uniformity of nature with regard to movement. He believed that “. . . the theory of what makes cells divide should not be very different from the theory of what makes muscle contract . . .” (Heilbrunn LV. The Dynamics of Living Protoplasm, 1956). He did not believe that one could understand how the living machine worked by investigating its parts. He believed that, to understand life, one must study the dynamics of living protoplasm. The origin and evolution of Heilbrunn’s thought process regarding the role of Ca2+ as a physiological activator will be traced back to the 1920s. The ways in which he tested the Ca2+ hypothesis in sea urchin eggs in the 1920s and 1930s will be explored. This work shaped Heilbrunn’s thinking about the role of Ca2+ in muscle contraction. Importantly, why he and his results were ignored for years will be examined. It turned out that being right was not enough. Bad luck and a stubborn belief in an outmoded scientific philosophy contributed to the neglect.

Stimulation of H+ secretion by CO2 in turtle bladder: role of intracellular pH, exocytosis, and calcium

1990 ◽  
Vol 258 (1) ◽  
pp. R222-R231
Author(s):  
J. A. Arruda ◽  
G. Dytko ◽  
Z. Talor
Keyword(s):  
Intracellular Calcium ◽  
Intracellular Ph ◽  
Fluorescent Dye ◽  
Isolated Cells ◽  
Cell Calcium ◽  
Turtle Bladder ◽  
Early Increase ◽  
Stimulation Of ◽  
Related Increase

We studied the interaction of intracellular pH, exocytosis, and cell calcium on the stimulation of H+ secretion by CO2 in turtle bladder. Intracellular pH was continuously monitored by the fluorescent dye 6-carboxyfluorescein and exocytosis was monitored by the release of mucosal fluorescein dextran. The initial stimulation of H+ secretion by 1 or 5% CO2 added to the serosal solution was accompanied by a similar and temporally related increase in exocytosis. Furthermore, a decrease in intracellular pH seems necessary for the early increase in H+ secretion and exocytosis. Because calcium plays an important role in exocytosis, we measured intracellular calcium in isolated cells with the fluorescent dye quin2. An increase in intracellular calcium (from 50 to 100 nM) was observed in isolated turtle bladder epithelial cells gassed with 5% CO2. To further evaluate the role of intracellular calcium on H+ secretion and exocytosis we utilized agents that alter cell calcium such as trifluoperazine and lanthanum. In the presence of CO2 these agents blocked partially the increase in H+ secretion and exocytosis but did not affect the decrease in intracellular H+. In conclusion, exocytosis, intracellular pH, and intracellular calcium play a key role in mediating CO2-stimulated H+ secretion in the turtle bladder.

Introductory Remarks

1980 ◽  
Vol 38 ◽  
pp. 598-599
Author(s):  
H. Mohri
Keyword(s):  
Muscle Contraction ◽  
Experimental Evidence ◽  
Sea Urchin ◽  
Constant Length ◽  
Thin Filaments ◽  
Bridge Formation ◽  
Thick Filaments ◽  
Sliding Mechanism ◽  
Radial Spokes ◽  
Cilia And Flagella

In 1959, Afzelius observed the presence of two rows of arms projecting from each outer doublet microtubule of the so-called 9 + 2 pattern of cilia and flagella, and suggested a possibility that the outer doublet microtubules slide with respect to each other with the aid of these arms during ciliary and flagellar movement. The identification of the arms as an ATPase, dynein, by Gibbons (1963)strengthened this hypothesis, since the ATPase-bearing heads of myosin molecules projecting from the thick filaments pull the thin filaments by cross-bridge formation during muscle contraction. The first experimental evidence for the sliding mechanism in cilia and flagella was obtained by examining the tip patterns of molluscan gill cilia by Satir (1965) who observed constant length of the microtubules during ciliary bending. Further evidence for the sliding-tubule mechanism was given by Summers and Gibbons (1971), using trypsin-treated axonemal fragments of sea urchin spermatozoa. Upon the addition of ATP, the outer doublets telescoped out from these fragments and the total length reached up to seven or more times that of the original fragment. Thus, the arms on a certain doublet microtubule can walk along the adjacent doublet when the doublet microtubules are disconnected by digestion of the interdoublet links which connect them with each other, or the radial spokes which connect them with the central pair-central sheath complex as illustrated in Fig. 1. On the basis of these pioneer works, the sliding-tubule mechanism has been established as one of the basic mechanisms for ciliary and flagellar movement.

scholarly journals A triple combination of treatments on moderate COVID-19

Open Medicine ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. 769-772
Author(s):  
ChunMiao Bao ◽  
BinBin Li ◽  
YuFeng Zhou
Keyword(s):  
Medical Records ◽  
Clinical Characteristics ◽  
Smoking Status ◽  
Length Of Hospital Stay ◽  
Convincing Evidence ◽  
Triple Combination ◽  
Viral Shedding ◽  
Null Effect ◽  
Treatment Start

Abstract Objective A triple combination of interferon (IFN) α-2b, lopinavir tablets, and umifenovir was used to treat COVID-19 patients. It is important to explore whether the benefit of this therapy is time dependent. Methods A cohort of moderate COVID-19 patients (n = 54) was admitted for hospitalization. The demographic (age, gender, and smoking status) and clinical characteristics (epidemiological trace and comorbidity) were collected from the digital medical records. The length of hospital stay (LOS) and the viral shedding time (VST) were set as the outcomes for COVID-19 cases. Results After control for age, sex, epidemiological trace, smoking, and comorbidity, the time of treatment start had null effect on VST (IRR = 1.09; 95% CI = 0.91–1.30; p = 0.33) or LOS (IRR = 1.10; 95% CI = 0.94–1.28; p = 0.23). Conclusion There is no convincing evidence to support a pivotal role of the timing of the therapy in the prognosis of moderate COVID-19 cases.

Regulation of intracellular calcium in N1E-115 neuroblastoma cells: the role of Na+/Ca2+exchange

2002 ◽  
Vol 282 (5) ◽  
pp. C1000-C1008 ◽  
Author(s):  
Kara L. Kopper ◽  
Joseph S. Adorante
Keyword(s):  
Membrane Potential ◽  
Intracellular Calcium ◽  
Normal Cell ◽  
Buffer Capacity ◽  
Neuroblastoma Cells ◽  
Fold Increase ◽  
Scorpion Venom ◽  
Reverse Mode ◽  
Intracellular Ca

In fura 2-loaded N1E-115 cells, regulation of intracellular Ca2+ concentration ([Ca2+]i) following a Ca2+ load induced by 1 μM thapsigargin and 10 μM carbonylcyanide p-trifluoromethyoxyphenylhydrazone (FCCP) was Na+ dependent and inhibited by 5 mM Ni2+. In cells with normal intracellular Na+ concentration ([Na+]i), removal of bath Na+, which should result in reversal of Na+/Ca2+exchange, did not increase [Ca2+]i unless cell Ca2+ buffer capacity was reduced. When N1E-115 cells were Na+ loaded using 100 μM veratridine and 4 μg/ml scorpion venom, the rate of the reverse mode of the Na+/Ca2+ exchanger was apparently enhanced, since an ∼4- to 6-fold increase in [Ca2+]ioccurred despite normal cell Ca2+ buffering. In SBFI-loaded cells, we were able to demonstrate forward operation of the Na+/Ca2+ exchanger (net efflux of Ca2+) by observing increases (∼ 6 mM) in [Na+]i. These Ni2+ (5 mM)-inhibited increases in [Na+]i could only be observed when a continuous ionomycin-induced influx of Ca2+ occurred. The voltage-sensitive dye bis-(1,3-diethylthiobarbituric acid) trimethine oxonol was used to measure changes in membrane potential. Ionomycin (1 μM) depolarized N1E-115 cells (∼25 mV). This depolarization was Na+dependent and blocked by 5 mM Ni2+ and 250–500 μM benzamil. These data provide evidence for the presence of an electrogenic Na+/Ca2+ exchanger that is capable of regulating [Ca2+]i after release of Ca2+ from cell stores.

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