Published online before print August 26, 2004, doi: 10.1161/01.RES.0000143014.04535.a3
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Submitted on December 18, 2003
Revised on July 26, 2004
Accepted on August 12, 2004
Function of Interstitial Cells of Cajal in the Rabbit Portal Vein
Maksym I. Harhun *;
From the Pharmacology and Clinical Pharmacology (M.I.H., D.V.G., O.V.P., T.B.B.), and Image Resource Facility (R.F.M.), Department of Basic Medical Sciences, St George’s Hospital Medical School, Cranmer Terrace, London, UK; Department of Nerve-Muscle Physiology (M.I.H., D.V.G., O.V.P.), A.A. Bogomoletz Institute of Physiology, Ukraine.
* To whom correspondence should be addressed. E-mail: mharhun{at}sghms.ac.uk.
Interstitial cells of Cajal (ICCs) were identified in the intact fixed media of the rabbit portal vein (RPV) using c-kit staining. The following experiments were performed using single cells preparations of the enzyme-dispersed vessel. Surviving contacts between the processes of single ICCs and the bodies of smooth muscle cells (SMCs) were observed in electron micrographs and by confocal microscopy. Spontaneous rhythmical [Ca2+]i oscillations were observed in ICCs after loading with the calcium indicator fluo-3 and were associated with depolarizations of the ICCs recorded by tight-seal patch pipette. To investigate signal transmission from ICCs to SMCs in dispersed cell pairs, or within small surviving fragments of the ICC network, an ICC was stimulated under voltage-clamp, while changes in [Ca2+]i in the stimulated cell as well as in a closely adjacent SMCs or ICCs were monitored using fast x-y confocal imaging of fluo-3 fluorescence. After stimulation of an single voltage-clamped ICC by a depolarizing step similar in duration to depolarizations associated with spontaneous [Ca2+]i oscillations, a depolarization and transient elevation of [Ca2+]i was observed in a closely adjacent SMCs after a delay of up to 4 seconds. In contrast, signal transmission from ICC to ICC was much faster, the delay being less than 200 ms. These results suggest that the an ICC may, in addition to generating an electrical signal (such as a slow wave) and thereby acting as a pacemaker for vascular SMCs of RPV, also releases some unknown diffusible substance, which depolarizes the SMCs.
Key words: interstitial cells of Cajal • rabbit portal vein • calcium waves • pacemaker activity • vascular smooth muscle
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