Effects of adrenergic receptor modulators on nuclear LCC‑channels in Purkinje neurons

Abstract

Large conductance cation channels (LCC‑channels), located in the nuclear membrane, are potential mediators of potassium (K+) countercurrent during calcium ion (Ca2+) release from intracellular stores. This study examined the effects of epinephrine, norepinephrine, isoprenaline, and propranolol on the electrophysiological properties of these channels to evaluate their potential as blocking agents in future studies of LCC‑channel involvement in Ca2+ release. The patch‑clamp method, using voltage‑clamp mode and a nucleus‑attached configuration, was employed to record currents passing through LCC‑channels in Purkinje cell nuclei. The effectiveness of Ca2+ blocking was estimated by analyzing changes in current amplitude and the probability of the channels being in an open state. All tested adrenergic receptor modulators decreased current amplitude through LCC‑channels at negative membrane potentials to varying extents, while no changes in amplitude were found for positive applied potentials for any compound. Epinephrine, norepinephrine, and propranolol demonstrated blocking capabilities comparable to nicotinic acetylcholine receptor (nAChR) modulators under similar conditions. Notably, only norepinephrine significantly inhibited the open‑state probability of LCC‑channels, whereas isoprenaline increased this parameter and induced rapid flickering. Furthermore, isoprenaline produced a greater reduction in current amplitude through LCC‑channels than the other compounds.