Modulation of cardiac inotropy: Contributions of diastolic [calcium(2+)], peak systolic [calcium(2+)] and calcium(2+) transient amplitudes to amplitudes of contraction in guinea pig ventricular myocytes.
Date
2006
Authors
Shutt, Robin Helena.
Journal Title
Journal ISSN
Volume Title
Publisher
Dalhousie University
Abstract
Description
Positive inotropy following rest, in elevated extracellular calcium (Ca 2+), during hypothermia or with increasing stimulation frequency has been attributed to increased sarcoplasmic reticulum (SR) Ca2+ content and/or increased trigger Ca2+. However, each of these manipulations also may elevate diastolic [Ca2+]. The objective of this study was to determine whether diastolic [Ca2+] could contribute to positive inotropy in isolated guinea pig ventricular myocytes at physiological temperatures (37°C). Intracellular [Ca2+] was measured with fura-2. Cell shortening was measured with an edge detector. SR Ca2+ stores were assessed by rapid application of 10 mM caffeine. Under voltage clamp conditions, when extracellular [Ca2+ ] was elevated contraction amplitude increased with increasing extracellular [Ca2+], in parallel with increasing diastolic and peak systolic Ca2+. Interestingly, Ca2+ transient amplitude did not increase. Furthermore, SR Ca2+ stores did not increase when extracellular [Ca2+] was elevated. Thus, positive inotropy occurred in the absence of changes in Ca2+ transient amplitude, indicating that diastolic Ca2+ may be an important contributor to positive inotropy. When voltage clamped myocytes were stimulated from rest similar results were found; diastolic Ca2+ and contraction amplitude increased while Ca2+ transient amplitude did not. Thus, these data suggest that diastolic Ca2+ is an important determinant of contraction amplitude. In contrast, both Ca2+ transient amplitude and diastolic Ca2+ increased in parallel with increasing contraction amplitude when rates of field stimulation were increased. Thus, when Ca2+ transient amplitude and diastolic Ca2+ both increased, positive inotropy occurred. In hypothermic myocytes (24°C) amplitudes of contractions, SR Ca 2+ stores and Ca2+ transients were increased with respect to 37°C, while diastolic Ca2+ did not change. Therefore positive inotropy also occurred when Ca2+ transient amplitude increased, in the absence of increasing diastolic Ca2+. Thus, the data presented in this thesis demonstrate that a change in either diastolic Ca2+ or Ca2+ transient amplitude was sufficient for positive inotropy to occur. Interestingly, when either diastolic Ca 2+ or Ca2+ transient amplitude increased, the peak systolic [Ca2+] achieved also was increased. Therefore, by influencing peak systolic Ca2+ both Ca2+ transient amplitude and diastolic Ca2+ could influence contraction amplitude.
Thesis (Ph.D.)--Dalhousie University (Canada), 2006.
Thesis (Ph.D.)--Dalhousie University (Canada), 2006.
Keywords
Health Sciences, Pharmacology., Biology, Physiology.