Effects of a physiological insulin concentration on the endothelin- sensitive Ca2+ store in porcine coronary artery smooth muscle

G. M. Dick, M. Sturek

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The effect of insulin to attenuate the Ca2+ and contractile response of vascular smooth muscle to a number of agonists has been described previously, but the Ca2+ regulatory mechanisms of insulin action remain unclear. We determined the effect of a physiological insulin concentration (300 pmol/l) on the Ca2+ response of vascular smooth muscle cells of the porcine right coronary artery to endothelin 1 (ET-1); furthermore, we examined the cellular Ca2+ stores affected by insulin (i.e., Ca2+ stores releasable by inositol 1,4,5-trisphosphate, caffeine, and ionomycin). We measured the Ca2+ responses of acutely isolated single smooth muscle cells with the fluorescent Ca2+ indicator Fura-2. Acute insulin exposure (20 min) significantly attenuated the Ca2+ response of single smooth muscle cells to 10 nmol/l ET-1. This inhibitory effect of insulin was observed both in the presence and absence of extracellular Ca2+. In contrast with the effects on ET-1-induced Ca2+ responses, insulin did not inhibit the Ca2+ response to 5 mmol/l caffeine, an agent that directly releases sarcoplasmic reticulum Ca2+ stores. Insulin was also without effect on the total cellular Ca2+ store released by 1 μmol/l ionomycin, a Ca2+-transporting ionophore. When ET-1 and caffeine were given in succession, a sizable caffeine-sensitive Ca2+ store could be released from insulin-treated cells but not control cells, indicating that the sarcoplasmic reticulum Ca2+ store of insulin- treated cells was not depleted by ET-1. Generalized depletion of the sarcoplasmic reticulum Ca2+ store is not one of the cellular mechanisms involved in the effect of insulin on coronary smooth muscle; instead, the effect may be due to an inhibitory influence on transmembrane signal transduction, such as diminished ET-1-induced inositol 1,4,5-trisphosphate production or reduced ability of this phosphoinositol to release stored Ca2+.

Original languageEnglish
Pages (from-to)876-880
Number of pages5
JournalDiabetes
Volume45
Issue number3 SUPPL.
DOIs
StatePublished - 1 Jan 1996

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