PubMed HealthSearch

PubMed · 8026702

Post-natal decrease in chronotropic sensitivity to acetylcholine in rat heart.

Abstract

1. The negative chronotropic effects of acetylcholine and carbachol on isolated rat right atria were examined at 0, 4, 8, and 16 weeks after birth. 2. Acetylcholine produced negative chronotropic responses at all ages and completely abolished spontaneous beating at its maximum effective concentration. 3. The sensitivity to acetylcholine, expressed in terms of ED50 values, was higher at 0 and 4 weeks than at 8 and 16 weeks, ED50 values (microM) at 0, 4, 8 and 16 weeks being 9.5 +/- 1.8 (n = 12), 13.2 +/- 3.4 (n = 11), 59.3 +/- 10.9 (n = 14) and 51.5 +/- 17.5 (n = 5), respectively. 4. Neostigmine produced a leftward shift of the concentration-response curve for acetylcholine both at 4 and 8 weeks after birth. The shift was larger at 8 weeks and no difference in sensitivity to acetylcholine was observed between the two ages in the presence of neostigmine. 5. Further, no developmental changes were observed in the sensitivity to carbachol, which is not hydrolyzed by cholinesterase. 6. We concluded that the chronotropic sensitivity to acetylcholine of rat atria decreases post-natally during the period between 4 and 8 weeks after birth due to increase in cholinesterase activity.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

H Tanaka, T Matsuda, H Kawada, K Shigenobu. 1994. Post-natal decrease in chronotropic sensitivity to acetylcholine in rat heart.. https://doi.org/10.1016/0306-3623(94)90026-4

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Relations between acetylcholine release and electrophysiological characteristics of theta rhythm: a microdialysis study in the urethane-anesthetized rat hippocampus.

In urethane-anesthetized rats, recording electrodes were implanted in the left dorsal hippocampus and a dialysis probe was placed in the contralateral dorsal or ventral hippocampus. Samples of extracellular acetylcholine (ACh) levels were assessed at 10-min intervals over a period of 30 min using microdialysis with high-performance liquid chromatography with electrochemical detection. EEG was recorded during the same period and amplitude, frequency, and duration of theta rhythm were calculated for each of the three 10-min intervals. Data were analyzed using the two-tailed Spearman rank-order correlation test. A positive and high rank correlation coefficient (rho = 0.90, p < 0.01, n = 8) was seen between the average ACh outflow in the dorsal hippocampus and the average theta amplitude, both being calculated for the entire collection period. A lower but statistically significant positive correlation (rho = 0.59, p < 0.01) between dorsal hippocampus ACh output and theta amplitude was also found when the couples of values collected for the 30-min period were pooled (n = 20). In contrast, frequency and duration of theta were not significantly correlated with dorsal hippocampus ACh release. Also, no statistically significant correlation (p > 0.05) was found between ACh output in the ventral hippocampus and theta parameters. Because changes in hippocampal ACh outflow are believed to be the reflection of changes in number and/or level of activity of cholinergic afferents to the dorsal hippocampus, our present findings support the view that, at least in the dorsal hippocampus of the urethane-anesthetized rat, the septohippocampal cholinergic projection regulates the theta amplitude but not frequency. Finally, the possibility that ACh outflow increase and tonic release in the hippocampus is not a sufficient condition to induce and maintain theta in the urethane-anesthetized rat is discussed.

Acetylcholine

Depletion of intracellular calcium stores activates a calcium conducting nonselective cation current in mouse pancreatic acinar cells.

Receptor-mediated Ca2+ release from inositol (1,4,5)-trisphosphate (IP3)-sensitive Ca2+ stores causes "capacitative calcium entry" in many cell types (Putney, J. W., Jr. (1986) Cell Calcium 7, 1-12; Putney, J. W., Jr. (1990) Cell Calcium 11, 611-624). We used patch-clamp and fluorescence techniques in isolated mouse pancreatic acinar cells to identify ion currents and cytosolic calcium concentrations under conditions in which intracellular Ca2+ stores were emptied. We found that depletion of Ca2+ stores activated a calcium-release-activated nonselective cation current (ICRANC) which did not discriminate between monovalent cations. ICRANC possessed a significant conductance for Ca2+ and Ba2+. It was not inhibited by La3+, Gd3+, Co2+, or Cd2+ but was completely abolished by flufenamic acid or genistein. In whole cell and cell-attached recordings, a 40-45 pS nonselective cation channel was identified which was activated by Ca2+ store depletion. Calcium entry as detected by single cell fluorescence measurements with fluo-3 or fura-2, showed the same pharmacological properties as ICRANC. We conclude that in mouse pancreatic acinar cells 40-45 pS nonselective cation channels serve as a pathway for capacitative Ca2+ entry. This entry pathway differs from the previously described ICRAC (Hoth, M., and Penner, R. (1992) Nature 355, 353-356) in its ion-selectivity, pharmacological profile, and single-channel conductance.

Acetylcholine