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[[alpha].sub.1D] L-type Ca channel was assumed to be of neuroendocrine origin only: however, [[alpha].sub.1D] L-type Ca channel knockout mice exhibit sinus bradycardia and atrioventricular block, indicating a distinct role of [[alpha].sub.1D] in the heart. The presence and distribution of [[alpha].sub.1D] Ca channel in the heart and its regulation by protein kinase A (PKA) are just emerging. Our objective was to examine the localization of [[alpha].sub.1D] L-type Ca channel in rabbit and rat hearts and its modulation by PKA. Here, we show the exclusive presence of [[alpha].sub.1D] Ca channel transcript in the sinoatrial node, atrio-ventricular node, and atria but not in the ventricle by RT-PCR and the expression of [[alpha].sub.1D] Ca channel protein in atrial myocytes' sarcolemma by indirect immunostaining and Western blot. There is no significant difference in the expression level of [[alpha].sub.1D] Ca channel in the left versus right atrium. Superfusion of membrane-permeable 8-bromo-cAMP resulted in a significant increase of the peak current density of [[alpha].sub.1D] Ca current expressed in tsA201 cells. This increase was inhibited by the PKA inhibitor (PKI). Application of 8-bromo-cAMP also readily phosphorylated the [[alpha].sub.1D] Ca channel protein. The results are first to demonstrate that PKA phosphorylation of L-type Ca channel [[alpha].sub.1D]-subunit resulted in an increase of the [[alpha].sub.1D] Ca channel activity. Together with the observation that [[alpha].sub.1D] Ca channel is exclusively present in the sinoatrial node and atria, the findings suggest that [[alpha].sub.1D] Ca channel plays a unique role in the sinoatrial tissue and is a target for sympathetic control of heart rhythm. phosphorylation; protein kinase A; sinoatrial node

Introduction: Cocaine has been shown to have broad cardiovascular effects that could be life threatening. Most of the reported electro-physiologic effects of cocaine have been studied in normal but not infarcted myocardium. Methods and Results: Using microelectrode techniques, we investigated the eletrophysiologic effects of cocaine on endocardial canine Purkinje fibers that survived 1 day of myocardial Infarction. In quiescent infarcted preparations, stimulated trains were followed by subthresh-old delayed afterdepolarizations (DADs), in the presence of propranolol (1 μM). Cocaine (10 μM) decreased the amplitude of DADs from 6.1 ± 1.8 mV to 3.0 ± 1.3 mV (P < 0.05, n = 6). When stimulated preparations (n = 23) showing no triggered activity during control (+propra-nolol) were superfused with a low concentration of caffeine (1 mM) or high extracellular Ca2+ (8.1 mM), triggered activity was Induced. Subsequent cocaine (10 μM) superfusion prevented the induction of caffeine- and high Ca2+-induced triggered activity. Cocaine's effects were reversible upon washout. In preparations that showed triggered activity during control conditions (+propranolol), the mean cycle length of triggered activity was 755 ± 45 msec. Cocaine (10 μM) superfusion lengthened the cycle length to 1030 ± 141 msec and terminated triggered activity with a subthreshold DAD (n = 12). In addition, cocaine and ryanodine (10 μM) suppressed triggered activity in a similar manner when tested in the same preparations (n = 4). During control conditions, cocaine did not cause any significant change on the rate of rise of action potential upstroke (from 55.6 ± 24.3 to 54.5 ± 28.6 V/sec, n = 8) and maximum diastolic potential (from -58.4 ± 4.3 to -56.6 ± 6.5 mV, n = 8). In the absence of propranolol, 50 μM but not 10 μM cocaine induced early afterdepolarizations in 62% of the preparations exhibiting triggered activity during control conditions. Conclusion: The results suggest that cocaine modulates DADs and triggered activity in infarcted endocardial fibers via direct inhibition of cyclic release of Ca2+ from sarcoplasmic reticulum (SR) independently from a local anesthetic or sympathomimetic effect. This SR inhibition could account for the myocardial depressant effect of cocaine. However, while cocaine suppressed DADs, its induction of EADs can precipitate malignant ventricular arrhythmias in the setting of cocaine overdose and infarction. [ABSTRACT FROM AUTHOR]

Threshold testing of cardiac rhythm devices is essential to monitoring the proper functioning of such devices (1). However, the currently method of applying multiple ECG leads to the patient is burdensome and time consuming (2). We are presenting a completely new way to perform cardiac rhythm device threshold testing using pulse oximetry. Twenty patients, with varying cardiac rhythm devices and pacing modes, were enrolled and had their atrial and ventricular thresholds tested. A comparison was made between simultaneous threshold determinations via the standard EGM based method and the new pulse oximetry based method. 75% of the ventricular threshold tested and 58% of the atrial thresholds tested were the same with the two testing methods. The remainder of the tests (25% of ventricular threshold and 42% of the atrial threshold tests) varied by +0.25 V. This study shows that pulse oximetry based testing is an accurate, reliable, and easy way to perform cardiac rhythm device threshold testing and may complement traditional methods to perform such tests in the future.