Functional impact of the hyperpolarization-activated current on the excitability of myelinated A-type vagal afferent neurons in the rat.

1. The hyperpolarization-induced, cation-selective current I(h) is widely observed in peripheral sensory neurons of the vagal and dorsal root ganglia, but the peak magnitude and voltage- and time-dependent properties of this current vary widely across afferent fibre type. 2. Using patch clamp investigations of rat isolated vagal ganglion neurons (VGN) identified as myelinated A-type afferents, we established a compendium of functional correlates between changes in membrane potential and the dynamic discharge properties of these sensory neurons as a result of the controlled recruitment of I(h) using the current clamp technique. 3. Two robust responses were observed in response to hyperpolarizing step currents: (i) upon initiation of the negative step current, there was a rapid hyperpolarization of membrane potential followed by a depolarizing voltage sag (DVS) towards a plateau in membrane potential as a result of steady state recruitment of I(h); and (ii) upon termination of the negative step current, there was a rapid return to the pretest resting membrane potential that often led to spontaneous action potential discharge. These data were strongly correlated (r(2) > 0.9) with a broad compendium of dynamic discharge characteristics in these A-type VGN. 4. In response to depolarizing step currents of increasing magnitude, the discharge frequency of the A-type VGN responded with increases in the rate of sustained repetitive discharge. Upon termination of the depolarizing step current, there was a post-excitatory membrane hyperpolarization of a magnitude that was strongly correlated with action potential discharge rate (r(2) > 0.9). 5. Application of the selective hyperpolarization-activated cyclic nucleotide gated (HCN) channel blockers ZD7288 (10 micromol/L) or CsCl (1.0 mmol/L) abolished I(h) and all of the aforementioned functional correlates. In addition to reducing the excitability of the A-type VGN to step depolarizing currents. 6. Because there is increasing evidence that the HCN channel current may represent a valid target for pharmacological intervention, the quantitative relationships described in the present study could potentially help guide the molecular and/or chemical modification of HCN channel gating properties to effect a particular outcome in VGN discharge properties, ideally well beyond merely selective blockade of a particular HCN channel subtype.

Hepatic angiomyolipoma: a clinical experience in diagnosis and treatment.

BACKGROUND: Hepatic angiomyolipoma is a rare mesenchyme-derived neoplasm often misdiagnosed as hepatocellular carcinoma, and the treatment for it remains controversial. AIMS: To develop the optimal preoperative diagnoses means and treatment modalities of hepatic angiomyolipoma. METHODS: Retrospective analysis of the clinical features, treatment, and prognostic data of 17 hepatic AML patients admitted to Chinese People's Liberation Army Generation Hospital between 1996 and 2006. RESULTS: Most hepatic angiomyolipoma were solitary. The overall preoperative diagnostic rate was 18% and the most common misdiagnosis was hepatocellular carcinoma (10/17, 59%). In three patients, observation was performed for 2-3 years before being admitted. The tumors increased 1-9 cm in size in all patients. All of the 17 patients finally received various liver resection procedures, and postoperative mortality and morbidity was 0 and 12% (2/17). After a median follow-up period of 73 months, the tumor recurred only in one patient 9 years post-operatively. CONCLUSIONS: Hepatic angiomyolipoma should be suspected in liver tumor patients with normal α-fetoprotein levels and no concomitant hepatitis. Preoperative MRI combined with percutaneous fine-needle biopsy should be the diagnostic methods of choice. Small hepatic AML proved through pathologic examination (<5 cm) may be managed by observation with close follow-up, but surgery is indicated in patients suffering from large tumors or significantly larger tumors during follow-up.