Cyclosporine A (CsA) is commonly used in immunosuppressivc therapy following organ transplantation. However, chronic treatment with CsA has been reported to result in hypertension due, in part, to an increase in sympathetic activation. The present study was designed to addresses the hypothesis that CsA modulation of baroreceptor neuronal activity is due to specific effects of CsA on baroreceptor neuron voltage-gated channels. Cardiopulmonary baroreceptor neurons (CpBN) were labeled via a pericardial sack injection of Oil and were isolated 4-5 days later. Standard whole-cell current clamp, voltage-clamp and cell-attached patch techniques were used to study the effects of CsA on the electrophysiological properties of these cells. CpBN action potentials were recorded in current-clamp configuration with 0 holding- current applied following either a 0.3 nA, 5.0 msec step current or a 0.3 nA, 100 msec step current. Resting membrane potential ranged between -48 and -62 mV (n=5). Application of 10 nM CsA resulted in a marked hyperpoiarization of the membrane potential with decrease in input resistance (n=4). To determine the effects of CsA on voltage-gated Ca++ and K+ channels, CpBNs were recorded under voltage-clamp conditions. Bath application of 10 nM CsA had no effect on CpBN voltage-gated Ca+ currents. Total K+ currents were recorded in the absence of Na+ and Ca++ currents by ion substitution and pharmacological blockade. Bath application of CsA (5 and 10 nM) increased the outward K+ current by 160.3±5% (n= 11/15). Additional single-channel studies suggest that application of CsA results in the activation of a BK type IKCa channel in these neurons. These results suggest one mechanisms for CsA sympathoexcitation may involve inhibition of baroreceptor afférents via activation of KCa channels.
|Original language||English (US)|
|Publication status||Published - 1996|
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- Biochemistry, Genetics and Molecular Biology(all)
- Cell Biology