A chloride current component induced by hypertrophy in rat ventricular myocytes

The effect of hypertrophy on membrane currents of rat left ventricular myocytes was studied with the whole cell voltage-clamp method. We found that the slope of the total time-independent current density-voltage relationship was increased in hypertrophied cells. No change in the zero-current potential was observed. Surprisingly, the dominant time-independent current, the inward rectifier K+ current (measured as the Ba(2+)-sensitive current density) was unchanged. We therefore investigated the identity of the outwardly rectifying Ba(2+)-resistant current seen in the hypertrophied rat ventricular myocytes but not present in control cells. We found that this current 1) was not carried by monovalent cations, 2) was partially blocked by anthracene-9-carboxylic acid (9-AC), and 3) was sensitive to variations in extracellular Cl concentration. These findings are consistent with the current being carried at least partially by Cl-. The presence of an additional Cl(-)-dependent component in hypertrophied cells is supported by the actions of 9-AC on the measured action potentials (APs). 9-AC had no effect on control cells APs but prolonged hypertrophied cell APs. We conclude that a Cl- current component develops in hypertrophied rat heart cells. This component appears to shorten the AP duration and might thus provide protection from cardiac arrhythmias.

Passive electrical properties of normal and hypertrophied rat myocardium

We determined the electrical constants of epicardial and endocardial preparations from both normal and hypertrophied rat hearts. This was done by comparative analysis of the spatial decay of steady-state electronic voltage deflection produced by injection of a hyperpolarizing constant-current pulse. We used a two-dimensional finite disk model to obtain the apparent membrane resistance, (Rm)app, and internal longitudinal resistivity (Ri), (Rm)app was significantly larger in epicardial (565 +/- 222 omega . cm2) than endocardial (375 +/- 137) preparations from normal hearts. This regional difference disappeared in hypertrophied hearts (epicardium 421 +/- 138, endocardium 383 +/- 121 omega . cm2). Ri was similar for normal endocardial (272 +/- 169 omega . cm) and epicardial (326 +/- 152) preparations, as well as for hypertrophied endocardial (251 +/- 108) and epicardial (312 +/- 59) preparations. We determined the effective membrane capacity (Ceff) by measuring the ratio of applied charge to the displacement of membrane potential. Ceff was larger for normal hearts (epicardium 9.7 +/- 2.5 micro F/cm2, endocardium 7.5 +/- 3.0) than for hypertrophied hearts (epicardium 4.1 +/- 1.4, endocardium 4.7 +/- 1.2). From the values for Ceff we calculated the effective membrane resistance, (Rm)eff. (Rm)eff was larger for normal (epicardium 5,392 +/- 2,613 omega . cm2, endocardium 3,013 +/- 2,096) than for hypertrophied (epicardium 1,552 +/- 633, endocardium 1,838 +/- 826) preparations. Our results show that the amount of electrically effective membrane area is decreased in hypertrophied myocardium, despite the increased total area per hypertrophied cell. One functional implication of this finding is that activation of contraction by spread of surface electrical depolarization into the T-tubules may be impaired in hypertrophied cardiac muscle.

Pancreatic Response to Bolus Injection of Cholecystokinin-pancreozymin in Anaesthetized and Conscious Rats Fed Raw Soyaflour

Pancreatic secretion was studied in rats fed raw soyaflour before (basal) and after stimulation with cholecystokinin-pancreozymin (CCK) given in either ascending or descending dose orders ranging from 1� 25 to 20 or from 20 to 1� 25 Crick-Harper-Raper units (CHRU). These results were compared with those reported previously for animals fed a stock cube diet. Two experimental conditions were used: anaesthetized animals were tested immediately after cannulation of the pancreatic duct and conscious animals were tested 48 h after surgery. Basal flow was significantly increased in anaesthetized and conscious rats fed RSF compared with the respective animals fed cubes. Mean basal protein output was also increased, but this difference was not significant. The pancreatic response to the ascending and descending doses of CCK in anaesthetized rats fed RSF was linearly related to the log of the dose of CCK in both animals fed RSF and cubes, though the response to CCK was greater in the rats fed RSF. When ascending doses of CCK were given to conscious rats fed RSF, the protein output increased up to 10 CHRU of CCK but was inhibited by 20 CHRU of CCK, whereas it decreased after the first dose of CCK (1�25 CHRU) in animals fed cubes. When descending doses of CCK were given to animals fed RSF, protein output was greatest after the first dose and no simple relationship between dose and response was seen. Compared with rats fed cubes, the pancreas in rats fed RSF thus appears to respond to a given dose of CCK with increased secretion, and conscious animals fed RSF can tolerate a higher dose of CCK before protein output is inhibited. This is consistent with an increased population of acinar cells in the animals fed RSF, with each hypertrophied cell responding to CCK with increased secretion.

Long-Term Evolution of the Main Changes Induced by Thioacetamide on Hepatocytes

The results of an electron microscopic study of the changes in hepatocytes induced by chronic intoxication with thioacetamide are reported. During the poisoning aspecific toxic changes are intermingled with progressive, preneoplastic ones. The main cell sub-populations identified are: 1) large hepatocytes with smooth endoplasmic reticulum (SER) hypertrophy, with or without rough endoplasmic reticulum (RER) neoformation and glycogen storage, which is starvation resistant; 2) smaller hepatocytes, where RER hypertrophy and ribosome accumulation are the prominent features. Such a pattern persists for months. After the withdrawal of the drug most of the cell changes disappear. However, during this time a simplification of the liver structure and cell composition takes place, allowing a sequence of cell events which seem relevant for establishment of neoplastic progression. The SER-hypertrophied cell appears first and gives rise, via several intermediate stages, to the RER-hypertrophied one, which is believed to play a key role as the ultimate precursor of cancer cells.