%0 Journal Article
%T Multiple ion channel block by the cation channel inhibitor SKF©\96365 in myocytes from the rabbit atrioventricular node
%A Alexander E. Curtis
%A Claire Fellingham
%A Hongwei Cheng
%A Jules C. Hancox
%J Archive of "Physiological Reports".
%D 2016
%R 10.14814/phy2.12819
%X The atrioventricular node (AVN) of the cardiac conduction system coordinates atrial¨Cventricular excitation and can act as a subsidiary pacemaker. Recent evidence suggests that an inward background sodium current, I B,Na, carried by nonselective cation channels (NSCCs), contributes to AVN cell pacemaking. The study of the physiological contribution of I B,Na has been hampered, however, by a lack of selective pharmacological antagonists. This study investigated effects of the NSCC inhibitor SKF©\96365 on spontaneous activity, I B,Na, and other ionic currents in AVN cells isolated from the rabbit. Whole©\cell patch©\clamp recordings of action potentials (APs) and ionic currents were made at 35¨C37¡ãC. A concentration of 10 ¦Ìmol/L SKF©\96365 slowed spontaneous action potential rate by 13.9 ¡À 5.3% (n = 8) and slope of the diastolic depolarization from 158.1 ¡À 30.5 to 86.8 ¡À 30.5 mV sec£¿1 (P < 0.01; n = 8). Action potential upstroke velocity and maximum diastolic potential were also reduced. Under I B,Na©\selective conditions, 10 ¦Ìmol/L SKF©\96365 inhibited I B,Na at £¿50 mV by 36.1 ¡À 6.8% (n = 8); however, effects on additional channel currents were also observed. Thus, the peak l©\type calcium current (I Ca,L) at +10 mV was inhibited by 38.6 ¡À 8.1% (n = 8), while the rapid delayed rectifier current, I Kr, tails at £¿40 mV following depolarization to +20 mV were inhibited by 55.6 ¡À 4.6% (n = 8). The hyperpolarization©\activated current, I f, was unaffected by SKF©\96365. Collectively, these results indicate that SKF©\96365 exerts a moderate inhibitory effect on I B,Na and slows AVN cell pacemaking. However, additional effects of the compound on I Ca,L and I Kr confound the use of SKF©\96365 to dissect out selectively the physiological role of I B,Na in the AVN
%K Atrioventricular node
%K AV node
%K AVN
%K background current
%K calcium current
%K hyperpolarization©\activated current
%K IB
%K Na
%K ICa
%K L
%K If
%K IKr
%K pacemaking
%K rapid delayed rectifier
%K SKF©\96365
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908495/