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Angiotensin II Induces Calcium-Dependent Rhythmic Activity in a Subpopulation of Rat Hypothalamic Median Preoptic Nucleus Neurons

¹Neurosciences Program, Ottawa Health Research Institute and University of Ottawa, Ottawa, Ontario, Canada; and ²Warwick Medical School, University of Warwick, Coventry, United Kingdom

Submitted 28 July 2004; accepted in final form 9 November 2004

Whole cell patch-clamp recordings revealed a subpopulation (16%, n = 18/112) of rat median preoptic nucleus (MnPO) neurons responded to bath-applied angiotensin II (Ang II; 100 nM to 5 µM; 30–90 s) with a prolonged TTX-resistant membrane depolarization and rhythmic bursting activity. At rest, cells characteristically displayed relatively low input resistance and negative resting potentials. Ang-II-induced responses featured increased input resistance, a reversal potential of –95 ± 2 mV, an increase in action potential duration from 2.9 ± 0.5 to 4.3 ± 0.8 ms, and the appearance of a rebound excitation at the offset of membrane responses to hyperpolarizing current injection. The latter was sensitive to Ni²⁺ (0.5–1 mM; n = 5), insensitive to extracellular Cs⁺ (1 mM, n = 7), and intracellular QX-314 (4 mM, n = 5), consistent with activation of a T-type Ca²⁺ conductance. Coincident with the Ang-II-induced depolarization was the appearance of rhythmic depolarizing shifts at a frequency of 0.14 ± 0.09 Hz with superimposed bursts of 4–22 action potentials interspersed with silent periods persisting for >1 h after washout. These TTX-resistant depolarizing shifts increased in amplitude and decreased in frequency with membrane hyperpolarization with activity ceasing beyond approximately –80mV, and were abolished in low-Ca²⁺/high-Mg²⁺ bathing medium (n = 6), Co²⁺ (1 mM; n = 6), or Ni²⁺ (0.5–1 mM; n = 8). Thus in a subpopulation of MnPO neurons, Ang II induces "pacemaker-like" activity by reducing a K⁺-dependent leak conductance that contributes to resting membrane potential and promoting of Ca²⁺-dependent regenerative auto-excitation mediated, in part, by a T-type Ca²⁺ conductance.

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