Angiotensin II induces calcium-dependent rhythmic activity in a subpopulation of rat hypothalamic median preoptic nucleus neurons.
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 microM; 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 -80 mV, and were abolished in low-Ca(2+)/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 Ca(2+)-dependent regenerative auto-excitation mediated, in part, by a T-type Ca2+ conductance.
Spanswick
David
D
Neurosciences Program, Ottawa Health Research Institute and University of Ottawa, 725 Parkdale Ave., Ottawa, Ontario, Canada K1Y 4E9.
Renaud
Leo P
LP
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D011301:Preoptic Area / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D020318:Rats, Long-Evans
D000804:Angiotensin II