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(Circulation Research. 2004;95:619.)
© 2004 American Heart Association, Inc.

Cellular Biology

Function of Interstitial Cells of Cajal in the Rabbit Portal Vein

Maksym I. Harhun, Dmitri V. Gordienko, Oleksandr V. Povstyan, Ray F. Moss, Thomas B. Bolton

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; and Department of Nerve-Muscle Physiology (M.I.H., D.V.G., O.V.P.), A.A. Bogomoletz Institute of Physiology, Ukraine.

Correspondence to Dr M.I. Harhun, Pharmacology and Clinical Pharmacology Basic Medical Sciences Department, St George’s Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK. 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 cell 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 SMC or ICCs were monitored using fast x-y confocal imaging of fluo-3 fluorescence. After stimulation of 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 release 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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