Within neurons, Ca2+-dependent inactivation (CDI) of voltage-gated L-type Ca2+ channels shapes cytoplasmic Ca2+ signals. CDI is initiated by Ca2+ binding to channel-associated calmodulin and subsequent Ca2+/calmodulin activation of the Ca2+-dependent phosphatase, calcineurin (CaN), which is targeted to L channels by the A-kinase-anchoring protein AKAP79/150. Here, we report that CDI of neuronal...

Mibefradil is a Ca2+ channel antagonist that inhibits both T-type and high-voltage-activated Ca2+ channels. We previously showed that block of high-voltage-activated channels by mibefradil occurs through the production of an active metabolite by intracellular hydrolysis. In the present study, we modified the structure of mibefradil to develop a nonhydrolyzable analog, (1S, 2S)-2-(2-(N-[(3-benzi...

Voltage-dependent Ca2+ channels are a major pathway for Ca2+ entry in neurons. We have studied the electrophysiological, pharmacological, and molecular properties of voltage-gated Ca2+ channels in motoneurons of the rat facial nucleus in slices of the brainstem. Most facial motoneurons express both low voltage-activated (LVA) and high voltage-activated (HVA) Ca2+ channel currents. The HVA curre...

We simulated mechanisms that increase Ca2+ transients with two models: the Luo-Rudy II model for guinea pig (GP) ventricle (GP model) representing long action potential (AP) myocytes and the rat atrial (RA) model exemplifying myocytes with short APs. The interventions were activation of stretch-gated cationic channels, increase of intracellular Na+ concentration ([Na+]i), simulated bet-adrenoce...

The prostate is a gland whose secretions contribute to the seminal fluids ejaculated upon activation of autonomic sympathetic nerves. In elder males, the prostate undergoes an increase in stroma mass and myogenic tone, leading to benign prostatic hyperplasia that occludes the proximal urethra and the presentation of various lower urinary tract symptoms that decrease their quality of life. This ...

With the use of the whole cell patch-clamp technique, multiple subtypes of voltage-activated calcium channels, as indicated by measuring Ba2+ currents, were pharmacologically identified in acutely dissociated intracardiac neurons from adult rats. All tested neurons that were held at -80 mV displayed only high-voltage-activated (HVA) Ca2+ channel currents that were completely blocked by 100 micr...

Voltage-dependent Ca2+ channels Cav1.2 (L type) and Cav2.1 (P/Q type) are expressed in vascular smooth muscle cells (VSMCs) and are important for the contraction of renal resistance vessels. In the present study we examined whether native renal VSMCs coexpress L-, P-, and Q-type Ca2+ currents. The expression of both Cav2.1a (P-type) and Cav2.1b (Q-type) mRNA was demonstrated by RT-PCR in renal ...

The electrophysiology of neonatal rat ventricular myocytes with and without hypertrophy has not been characterized. The α1-adrenergic agonist phenylephrine induced hypertrophy in neonatal rat ventricular myocytes. After 48 h of exposure to 20 μM phenylephrine, cell surface area of hypertrophied myocytes was 44% larger than control. Action potential duration was significantly longer in hypertrop...

BACKGROUND Embryonic hearts exhibit spontaneous electrical activity, which depends on Ca2+ influx through L-type Ca2+ channels. In this study the expression of the L-type Ca2+ channel alpha1 subunit gene in the developing mouse heart was investigated. METHODS AND RESULTS Mouse cardiac ventricles 9.5 days post coitum (dpc), 18 dpc and adult were used. At 9.5 dpc the level of Cav1.3 mRNA was hi...