Cellular distribution of calcium current is unaltered during compensated hypertrophy in the spontaneously hypertensive rat.
Changes in cellular calcium (Ca(2+)) handling are thought to underlie the altered contraction that occurs during cardiac hypertrophy and failure. Recent work has highlighted the importance of t-tubules in the control of intracellular Ca(2+). The present study was performed to investigate whether changes in the distribution of I (Ca) between the surface and t-tubule membranes might contribute to the altered Ca(2+) handling observed during compensated hypertrophy in the spontaneously hypertensive rat (SHR). Experiments were performed on ventricular myocytes isolated from 5-month-old SHR and normotensive Wistar-Kyoto (WKY) control rats. Osmotic shock using formamide was used to disrupt the t-tubular system and the whole-cell patch clamp technique used to monitor I (Ca) in the presence and absence of t-tubules. Membrane capacitance and I (Ca) were greater in control SHR than WKY myocytes; following detubulation, cell capacitance and I (Ca) both decreased and were no longer significantly different in the two cell types. The density of I (Ca) was not significantly different in control SHR and WKY cells or in detubulated myocytes from the two species. These data suggest that the distribution of I (Ca) is unchanged in SHR myocytes compared to WKY controls; I (Ca) density in the t-tubules was 1.2-fold greater than in the sarcolemma in both strains. These data also imply that the increase in surface area in SHR myocytes is due principally to an increase in t-tubular area, which is accompanied by an approximately equivalent increase in I (Ca), so that the density of I (Ca) at the cell surface and in the t-tubules remains the same. These changes would be expected to retain cell function and synchronicity of Ca(2+) release in the SHR at this stage of compensated hypertrophy.
Fowler
Mark R
MR
Institute of Biomedical and Life Sciences, West Medical Building, University of Glasgow, Glasgow, G12 8QQ, UK.
Orchard
Clive H
CH
Harrison
Simon M
SM
D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism / Q000502:physiology*; D048429:Cell Size; D002478:Cells, Cultured; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity
D015220:Calcium Channels; D002118:Calcium