Stimulation of β-adrenoceptors inhibits store-operated channel currents via a cAMP-dependent protein kinase mechanism in rabbit portal vein myocytes

Previously we have described the properties of store-operated channel currents (SOCs) in freshly dispersed rabbit portal vein smooth muscle cells. In addition to Ca²⁺ store depletion these SOCs could also be activated by α-adrenoceptor stimulation and diacylglycerol (DAG) via a protein kinase C (PKC)-dependent mechanism. In the present study we have investigated the effect of β-adrenoceptor stimulation on SOCs in rabbit portal vein myocytes. With whole-cell recording the selective β-adrenoceptor agonist isoprenaline reduced the current evoked by cyclopiazonic acid (CPA, sarcoplasmic/endoplasmic reticulum ATPase inhibitor) by over 85%. With cell-attached patch recording, bath application of isoprenaline produced a pronounced inhibition of SOC activity evoked by either CPA or the acetoxymethyl ester form of BAPTA (BAPTA-AM). SOC activity evoked by CPA, the DAG analogue, 1-oleoyl-acetyl- sn -glycerol (OAG) or the phorbol ester, phorbol-12,13-dibutyrate (PDBu) was also markedly inhibited by the adenylate cyclase activator, forskolin, and the cell-permeable non-hydrolysable analogue of cyclic adenosine monophosphate (cAMP), 8-Br-cAMP. With inside-out patches, bath application of PDBu evoked channel currents with similar properties to SOCs which were inhibited by over 90% by a catalytic subunit of protein kinase A (PKA) and by 8-Br-cAMP. Moreover bath application of PKA inhibitors, H-89, KT5720 and an inhibitory peptide to quiescent cell-attached or inside-out patches, activated channel currents with similar properties to SOCs. These data suggest that in rabbit portal vein myocytes, stimulation of β-adrenoceptors inhibits SOC activity via a cAMP-dependent protein kinase signal transduction cascade. In addition it is concluded that constitutive PKA activity has a profound inhibitory effect on SOC activity in this vascular preparation.     

Suprameatal extension of the retrosigmoid approach: microsurgical anatomy

OBJECTIVE: This study was conducted to determine whether removing the bony prominence located above the porus of the internal acoustic meatus, called the suprameatal tubercle, and surrounding bone using the retrosigmoid approach would aid in the exposure of tumors that are located predominantly in the cerebellopontine angle but that also extend into the middle cranial fossa in the region of Meckel's cave and thus avoid the need for a supratentorial craniotomy. METHODS: Thirty cerebellopontine angles from 15 cadaveric heads examined using 3 to 40x magnification provided the material for this study. A retrosigmoid craniotomy was completed and the exposure obtained before and after removing the suprameatal tubercle, and the surrounding bone was examined. In some cases, Meckel's cave and the tentorium lateral to the porus of Meckel's cave was opened to aid in the exposure. RESULTS: Removing the suprameatal tubercle and surrounding bone increased the exposure an average of 10.3 mm (range, 8.0-13.0 mm) forward of the exposure, which could be obtained without suprameatal drilling. The extent of bone removal was limited on the lateral side by the posterior and superior semicircular canals and their common crus. CONCLUSION: The suprameatal extension of the retrosigmoid approach will permit removal of some tumors that are located mainly in the posterior fossa but that extend into the middle fossa in the region of Meckel's cave. The exposure can be increased by opening the superior petrosal sinus as it crosses in the upper margin of the porus of Meckel's cave and by opening the tentorium lateral to Meckel's cave.     

Telovelar approach to the fourth ventricle: microsurgical anatomy

OBJECT: In the past, access to the fourth ventricle was obtained by splitting the vermis or removing part of the cerebellum. The purpose of this study was to examine the access to the fourth ventricle achieved by opening the tela choroidea and inferior medullary velum, the two thin sheets of tissue that form the lower half of the roof of the fourth ventricle, without incising or removing part of the cerebellum. METHODS: Fifty formalin-fixed specimens, in which the arteries were perfused with red silicone and the veins with blue silicone, provided the material for this study. The dissections were performed in a stepwise manner to simulate the exposure that can be obtained by retracting the cerebellar tonsils and opening the tela choroidea and inferior medullary velum. CONCLUSIONS: Gently displacing the tonsils laterally exposes both the tela choroidea and the inferior medullary velum. Opening the tela provides access to the floor and body of the ventricle from the aqueduct to the obex. The additional opening of the velum provides access to the superior half of the roof of the ventricle, the fastigium, and the superolateral recess. Elevating the tonsillar surface away from the posterolateral medulla exposes the tela, which covers the lateral recess, and opening this tela exposes the structure forming the walls of the lateral recess.