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Electrophysiological effects of calcitonin gene‐related peptide in bull‐frog and guinea‐pig atrial myocytes.
Author(s) -
Ono K,
Giles W R
Publication year - 1991
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1991.sp018546
Subject(s) - calcitonin gene related peptide , medicine , electrophysiology , guinea pig , endocrinology , repolarization , patch clamp , myocyte , inward rectifier potassium ion channel , chemistry , membrane potential , biology , neuropeptide , biophysics , ion channel , receptor
1. Electrophysiological effects of calcitonin gene‐related peptide (CGRP) on action potentials and corresponding transmembrane currents in single myocytes from bull‐frog and guinea‐pig atria were studied using a whole‐cell voltage‐clamp method. 2. CGRP at relatively low concentrations increased the height of the action potential plateau in a dose‐dependent manner in both bull‐frog and guinea‐pig myocytes. In addition, in bull‐frog cells CGRP accelerated the early phase of repolarization, thus shortening the overall duration of the action potential. In contrast, in guinea‐pig myocytes CGRP prolonged the action potential duration at all concentrations that were studied. 3. Voltage‐clamp measurements demonstrated that CGRP increased transmembrane calcium current (ICa) in guinea‐pig myocytes without a significant change in its voltage dependence. The ED50 value for this effect on ICa was 1.28 +/‐ 0.55 X 10(‐8) M (n = 4). The time course of the inactivation of ICa was not affected by CGRP. 4. CGRP increased the delayed rectifier K+ current (IK) at relatively low concentrations in bull‐frog atria, whereas relatively high concentrations were needed to increase IK in guinea‐pig myocytes. This effect was observed even after complete inhibition of ICa. 5. CGRP had no significant effect on the inwardly rectifying background K+ current, IK1, even at very high concentrations. 6. Comparison of the time course of ICa augmentation in bull‐frog and guinea‐pig myocytes revealed an important difference in the effect of CGRP in these two types of cells. CGRP at maximal concentrations increased ICa transiently in bull‐frog myocytes, whereas this response was sustained in guinea‐pig myocytes. Isoprenaline (Iso) induced sustained increase in ICa in both species. When ICa was fully activated by Iso, CGRP at high concentrations strongly inhibited ICa in the bull‐frog, whereas it had little effect on ICa in guinea‐pig myocytes. 7. Intracellular application of GTP gamma S (guanosine 5'‐O‐(3‐thiotriphosphate) 10(‐4) M) greatly potentiated the CGRP effect on ICa; in contrast, GDP beta S (guanosine 5'‐O‐(2‐thiodiphosphate), 2 x 10(‐3) M) partially inhibited the CGRP‐induced augmentation of ICa. Taken together, these results indicate that the stimulation of ICa by CGRP is mediated by a GTP‐binding protein. 8. The observed dose‐dependent changes in ICa and IK in bull‐frog and guinea‐pig myocytes can explain the different patterns of CGRP‐induced changes in action potential shape in these two myocyte preparations.