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Articles in PresS, published online ahead of print November 27, 2001
Am J Physiol Cell Physiol, 10.1152/ajpcell.00393.2001
Submitted on August 10, 2001
Accepted on November 21, 2001
1 Pharmacology & Clinical Pharmacology, St George's Hospital Medical School, London, London, United Kingdom
* To whom correspondence should be addressed. E-mail: iain{at}physio.unr.edu.
Voltage-clamp studies of freshly isolated smooth muscle cells from rabbit portal vein revealed the existence of a time-dependent cation current evoked by membrane hyperpolarization (termed Ih). Half-maximal activation of Ih was about -105 mV with conventional whole cell and -80 mV when the perforated patch technique was used. Ih was augmented by an increase in extracellular K+ and was blocked rapidly by Cs+ (1-5 mM). The putative bradycardic agent ZD 7288 produced a characteristically slow inhibition of Ih. The depolarizing sag recorded in current clamp was also abolished by application of 5 mM Cs+. Cs+ significantly decreased the frequency of spontaneous contractions in both whole rat portal vein and rabbit portal vein segments. RT-mPCR of rabbit portal vein myocytes using primers derived from existing genes for hyperpolarization-activated cation channels (HCN 1-4) revealed the existence of cDNA clones corresponding to HCN2, 3 and 4. The present study shows that portal vein myocytes contain genes shown to encode for hyperpolarization-activated channels and exhibit an endogenous current with characteristics similar to Ih in other cell types. This conductance appears to determine partially the rhythmicity of this vessel.
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