Novel Single-Staged Posterior Retropleural Approach with Thoracoscopic Guidance for Resection of a Thoracic Dumbbell Schwannoma.

Dumbbell spinal cord tumors are infrequent pathologic entities. The optimal approach to safe surgical resection is ill-defined and must often be individualized. This is assisted with multiple tumor classification systems. Here, we describe a novel technique used to safely and successfully resect a large thoracic dumbbell schwannoma originating from the left T3 spinal nerve root with extension into the posterior mediastinum adjacent to the parietal pleura and thoracic aorta. A review of the literature was performed to study described surgical approaches to primary spinal dumbbell tumors. The decision-making process and preoperative imaging for operative planning are included. A detailed description of the procedure follows with intraoperative images. Gross total resection with no neurologic sequelae was achieved. Previously described operative techniques for resection of primary spinal dumbbell tumors with advantages and limitations of each are then reviewed. Gross total resection was safely achieved utilizing a single-staged posterior retropleural approach with anterior thoracoscopic guidance. The tumor was removed en bloc through a large posterior window. The prone position was utilized for the entire case with no intraoperative repositioning required. No intraoperative or immediate postoperative complications occurred. We report a novel approach to resecting a large primary spinal dumbbell tumor. A single-stage retropleural approach with anterior thoracoscopic guidance facilitated safe and successful gross total resection. Maintenance of the prone position throughout surgery allowed for reduced operative time, excellent anterior, and posterior visualization and no added patient morbidity. Repositioning to the lateral decubitus position may not be required in select cases.

SAP97 regulates Kir2.3 channels by multiple mechanisms.

We examined the impact of coexpressing the inwardly rectifying potassium channel, Kir2.3, with the scaffolding protein, synapse-associated protein (SAP) 97, and determined that coexpression of these proteins caused an approximately twofold increase in current density. A combination of techniques was used to determine if the SAP97-induced increase in Kir2.3 whole cell currents resulted from changes in the number of channels in the cell membrane, unitary channel conductance, or channel open probability. In the absence of SAP97, Kir2.3 was found predominantly in a cytoplasmic, vesicular compartment with relatively little Kir2.3 localized to the plasma membrane. The introduction of SAP97 caused a redistribution of Kir2.3, leading to prominent colocalization of Kir2.3 and SAP97 and a modest increase in cell surface Kir2.3. The median Kir2.3 single channel conductance in the absence of SAP97 was approximately 13 pS, whereas coexpression of SAP97 led to a wide distribution of channel events with three distinct peaks centered at 16, 29, and 42 pS. These changes occurred without altering channel open probability, current rectification properties, or pH sensitivity. Thus association of Kir2.3 with SAP97 in HEK293 cells increased channel cell surface expression and unitary channel conductance. However, changes in single channel conductance play the major role in determining whole cell currents in this model system. We further suggest that the SAP97 effect results from SAP97 binding to the Kir2.3 COOH-terminal domain and altering channel conformation.

Amino terminal glutamate residues confer spermine sensitivity and affect voltage gating and channel conductance of rat connexin40 gap junctions.

Connexin40 (Cx40) contains a specific binding site for spermine (affinity approximately 100 microm) whereas connexin43 (Cx43) is unaffected by identical concentrations of intracellular spermine. Replacement of two unique glutamate residues, E9 and E13, from the cytoplasmic amino terminal domain of Cx40 with the corresponding lysine residues from Cx43 eliminated the block by 2 mm spermine, reduced the transjunctional voltage (V(j)) gating sensitivity, and reduced the unitary conductance of this Cx40E9,13K gap junction channel protein. The single point mutations, Cx40E9K and Cx40E13K, predominantly affected the residual conductance state (G(min)) and V(j) gating properties, respectively. Heterotypic pairing of Cx40E9,13K with wild-type Cx40 in murine neuro2A (N2A) cells produced a strongly rectifying gap junction reminiscent of the inward rectification properties of the Kir (e.g. Kir2.x) family of potassium channels. The reciprocal Cx43K9,13E mutant protein exhibited reduced V(j) sensitivity, but displayed much less rectification in heterotypic pairings with wtCx43, negligible changes in the unitary channel conductance, and remained insensitive to spermine block. These data indicate that the connexin40 amino terminus may form a critical cytoplasmic pore-forming domain that serves as the receptor for V(j)-dependent closure and block by intracellular polyamines. Functional reciprocity between Cx40 and Cx43 gap junctions involves other amino acid residues in addition to the E or K 9 and 13 loci located on the amino terminal domain of these two connexins.

Regulation of connexin43 gap junctional conductance by ventricular action potentials.

Transjunctional voltage regulates cardiac gap junctional conductance, but the kinetics of inactivation were considered too slow to affect cardiac action potential propagation. Connexin43 (Cx43) is abundantly expressed in the atrial and ventricular myocardium and the rapid ventricular conduction tissues (ie, His-Purkinje system) of the mammalian heart and is important to conduction through these cardiac tissues. The kinetics of Cx43 voltage gating were examined at peak action potential voltages using simulated ventricular myocardial action potential waveforms or pulse protocols exceeding 100-mV transjunctional potentials. Junctional current responses approximate the action potential morphology but conductance calculations reveal a 50% to 60% decline from peak to near constant plateau values. Junctional conductance recovers during phase 3 repolarization and early diastole to initial values. The bases for these transient changes in junctional conductance are the rapid decay kinetics in tens of milliseconds at peak transjunctional voltages (Vj) of 130 mV and the gradual increase in junctional conductance as Vj returns toward 0 mV. The decay time constants change e-fold per 22.1 mV above the half-inactivation voltage for Cx43 gap junctions of +/-58 mV. A realistic dynamic model for changes in junctional resistance between excitable and nonexcitable cells during cardiac action potential propagation was developed based on these findings. This dynamic model of cardiac gap junctions will further our understanding of the role gap junctions play in the genesis and propagation of cardiac arrhythmias. The full text of this article is available online at http://www.circresaha.org.