Characteristics of hyperpolarization-activated cation currents in portal vein smooth muscle cells.
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 I(h)). Both the rate of activation and the amplitude of I(h) were enhanced by membrane hyperpolarization. Half-maximal activation of I(h) was about -105 mV with conventional whole cell and -80 mV when the perforated patch technique was used. In current clamp, injection of hyperpolarizing current produced a marked depolarizing "sag" followed by rebound depolarization. Activation of I(h) was augmented by an increase in the extracellular K(+) concentration and was blocked rapidly by externally applied Cs(+) (1-5 mM). The bradycardic agent ZD-7288 (10 microM), a selective inhibitor of I(h), produced a characteristically slow inhibition of the portal vein I(h). 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. Multiplex RT-PCR of rabbit portal vein myocytes using primers derived from existing genes for hyperpolarization-activated cation channels (HCN1-4) 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 I(h) in other cell types. This conductance appears to determine, in part, the rhythmicity of this vessel.
Greenwood
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Department of Pharmacology and Clinical Pharmacology, St. George's Hospital Medical School, London, SW17 0RE UK. i.greenwood@sghms.ac.uk
Prestwich
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D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D002412:Cations / Q000378:metabolism; D002586:Cesium / Q000494:pharmacology; D054815:Cyclic Nucleotide-Gated Cation Channels; D015870:Gene Expression / Q000502:physiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009124:Muscle Proteins; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011169:Portal Vein / Q000166:cytology* / Q000378:metabolism*; D011188:Potassium / Q000493:pharmacokinetics; D015221:Potassium Channels; D011743:Pyrimidines / Q000494:pharmacology; D011817:Rabbits; D012964:Sodium / Q000493:pharmacokinetics
D002317:Cardiovascular Agents; D002412:Cations; D054815:Cyclic Nucleotide-Gated Cation Channels; C578665:HCN1 protein, human; C578710:HCN2 protein, human; C119587:HCN4 protein, human; C578667:Hcn1 protein, rat; C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D009124:Muscle Proteins; D015221:Potassium Channels; D011743:Pyrimidines; C082246:ICI D2788; D002586:Cesium; D003994:Bucladesine; D012964:Sodium; D011188:Potassium