Norepinephrine Causes a Biphasic Change in Mammalian Pinealocye Membrane Potential: Role of α1B-Adrenoreceptors, Phospholipase C, and Ca2+

Perforated patch clamp recording was used to study the control of membrane potential (Vm) and spontaneous electrical activity in the rat pinealocyte by norepinephrine. Norepinephrine did not alter spiking frequency. However, it was found to act through α1B-adrenoreceptors in a concentration-dependent manner (0.1–10 μm) to produce a biphasic change in Vm. The initial response was a hyperpolarization (∼13 mV from a resting potential of −46 mV) due to a transient (∼5 sec) outward K+ current (∼50 pA). This current appears to be triggered by Ca2+ released from intracellular stores, based on the observation that it was also seen in cells bathed in Ca2+-deficient medium. In addition, pharmacological studies indicate that this current was dependent on phospholipase C (PLC) activation and was in part mediated by bicuculline methiodide and apamin-sensitive Ca2+-controlled K+ channels. The initial transient hyperpolarization was followed by a sustained depolarization (∼4 mV) due to an inward current (∼10 pA). This response was dependent on PLC-dependent activation of Na+/Ca2+ influx but did not involve nifedipine-sensitive voltage-gated Ca2+ channels. Together, these results indicate for the first time that activation of α1B-adrenoreceptors initiates a PLC-dependent biphasic change in pinealocyte Vm characterized by an initial transient hyperpolarization mediated by a mixture of Ca2+-activated K+ channels followed by a sustained depolarization mediated by a Ca2+-conducting nonselective cation channel. These observations indicate that both continuous elevation of intracellular Ca2+ and sustained depolarization at approximately −40 mV are associated with and are likely to be required for activation of the pinealocyte.