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Maria Gomez

Maria Gomez

Professor

Maria Gomez

Calcium channel activity and force regulation in smooth muscle: Effects of polyamines and growth stimulation.

Author

  • Maria Gomez

Summary, in English

The initial signal for contraction in smooth muscle is an increase in [Ca2+]i. Ca2+ ions can either enter the cytosol from the extracellular medium or be released from intracellular stores. Voltage-operated Ca2+ channels (VOC) play a dominant role in the activation of smooth muscle contraction. This thesis describes two novel regulatory mechanisms of the dihydropyridine (DHP)-sensitive VOC in smooth muscle. One of them involves the polyamines spermine (SP) and spermidine (SPD), and the other, a Ca2+-dependent modulation brought about by growth stimulation with foetal calf serum (FCS). The polyamines SP and SPD, ubiquitous polycations associated with cell growth and differentiation, inhibited electrical membrane activity and contraction in intestinal and vascular smooth muscle. We showed in guinea-pig ileum that this was due to inhibition of current through L-type Ca2+ channels. SP and SPD also increased Ca2+ sensitivity of the contractile system. Culture with the adenosylmethionine decarboxylase antagonist CGP 48664 reduces SP and SPD contents by more than 50 % and causes enhanced Ca2+ channel activity. This is consistent with increased spontaneous activity observed after culture with CGP 48664. Culture of intestinal smooth muscle with FCS reduced sensitivity of force to extracellular Ca2+ by a functional decrease in Ca2+ channel density. Downregulation of inward current was mediated by an increased [Ca2+]i, since it was reversed by the Ca2+ channel blocker verapamil and mimicked by the Ca2+ ionophore ionomycin. We conclude that the increased [Ca2+]i brought about by culture with FCS gives rise to a persistent and trophic modulation of L-type Ca2+ channel, in contrast to the direct modulation exerted by altered endogenous polyamines.

Department/s

  • Cardiovascular Research - Immunity and Atherosclerosis

Publishing year

1998

Language

English

Document type

Dissertation

Publisher

Sölvegatan 19, S223 62 Lund

Topic

  • Cardiac and Cardiovascular Systems

Keywords

  • verapamil
  • tissue culture
  • portal vein
  • patch-clamp
  • calcium
  • spermidine
  • spermine
  • polyamines
  • excitation-contraction
  • smooth muscle
  • calcium channel
  • ionomycin.
  • Physiology
  • Fysiologi

Status

Published

Research group

  • Cardiovascular Research - Immunity and Atherosclerosis

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISBN: 91-628-3076-7
  • ISRN: LUMED/MEFN--18--SE

Defence date

2 October 1998

Defence time

10:15

Defence place

Segerfalksalen, Wallenberg Neuroscience Center, Sölvegatan 17, Lund

Opponent

  • Alison M. Gurney (Prof)