A 170,000-Da glycoprotein (P170 multidrug transporter) becomes specifically labeled in multidrug-resistant human KB carcinoma cells by the photolabile lipophilic membrane probe 5-[125I]iodonaphthalene-1-azide ([125I]INA) when photoactivation of the probe is triggered by energy transfer from intracellular doxorubicin or rhodamine 123. In contrast, in drug-sensitive cells, drug-induced specific l...

The proinflammatory cytokine interleukin-1beta (IL-1beta) mediates inflammation and hyperalgesia, although the underlying mechanisms remain elusive. To better understand such molecular and cellular mechanisms, we investigated how IL-1beta modulates the total voltage-dependent sodium currents (INa) and its tetrodotoxin-resistant (TTX-R) component in capsaicin-sensitive trigeminal nociceptive neu...

Liu, Lieju, T. M. Yang, Wolfgang Liedtke, and S. A. Simon. Chronic IL-1 signaling potentiates voltage-dependent sodium currents in trigeminal nociceptive neurons. J Neurophysiol 95: 1478–1490, 2006. First published November 30, 2005; doi:10.1152/jn.00509.2005. The proinflammatory cytokine interleukin-1 (IL-1 ) mediates inflammation and hyperalgesia, although the underlying mechanisms remain elu...

Flecainide block of Na current (INa) was investigated in wildtype (WT) or the long QT syndrome 3 (LQT3) sodium channel a subunit mutation with three amino acids deleted (DKPQ) stably transfected into human embryonic kidney 293 cells using whole-cell, patch-clamp recordings. Flecainide (1–300 mM) caused tonic and use-dependent block (UDB) of INa in a concentration-dependent manner. Compared with...

Saeki, Tomoaki, Jian-Bing Shen, and Achilles J. Pappano. Carbachol promotes Na1 entry and augments Na/Ca exchange current in guinea pig ventricular myocytes. Am. J. Physiol. 273 (Heart Circ. Physiol. 42): H1984–H1993, 1997.— The effect of carbachol (CCh) on the Na/Ca exchange current (INa/Ca) was studied in voltage-clamped ventricular myocytes isolated from guinea pig hearts and superfused with...

BACKGROUND Drugs are screened for delayed rectifier potassium current (IKr) blockade to predict long QT syndrome prolongation and arrhythmogenesis. However, single-cell studies have shown that chronic (hours) exposure to some IKr blockers (eg, dofetilide) prolongs repolarization additionally by increasing late sodium current (INa-L) via inhibition of phosphoinositide 3-kinase. We hypothesized t...

The diuretic agent indapamide has been reported to block the slow component of the delayed rectifier K+ current (IKs) without altering the rapid component (IKr) or the inward rectifier current and has been used as a pharmacological probe for IKs; however, the effects of indapamide on Na+ (INa), L-type Ca2+ (ICa), and transient outward K+ (Ito) currents have not been determined. We applied tight...

BACKGROUND Brugada syndrome (BrS) primarily associates with the loss of sodium channel function. Previous studies showed features consistent with sodium current (INa) deficit in patients carrying desmosomal mutations, diagnosed with arrhythmogenic cardiomyopathy (or arrhythmogenic right ventricular cardiomyopathy). Experimental models showed correlation between the loss of expression of desmoso...

Hu, Xiu-Ti, Yan Dong, Xu-Feng Zhang, and Francis J. White. Dopamine D2 receptor-activated Ca 2 signaling modulates voltagesensitive sodium currents in rat nucleus accumbens neurons. J Neurophysiol 93: 1406–1417, 2005 doi:10.1152/jn.00771.2004. Receptor-mediated dopamine (DA) modulation of neuronal excitability in the nucleus accumbens (NAc) has been shown to be critically involved in drug addic...