Norepinephrine modulates high voltage-activated calcium channels in freshly dissociated rat nucleus tractus solitarii...

The effects of norepinephrine on the low- and high-voltage-activated calcium channels in the neurons acutely dissociated from the nucleus tractus solitarius of 2- to 3-week-old rats were investigated in the nystatin perforated patch recording configuration under voltage-clamp conditions. The norepinephrine had no effect on the low voltage-activated calcium channel but inhibited the high voltage-activated calcium channel in a concentration-, time- and voltage-dependent manner. The norepinephrine slowed the activation phase of the high voltage-activated calcium channel current and the maximum inhibition was 30% of the total current amplitude measured 10 ms after the current activation. The inhibitory effect was eliminated by applying larger depolarizing prepulses. The pretreatment with pertussis toxin completely blocked the norepinephrine effect on high-voltage activated calcium channels, suggesting the contribution of pertussis toxin-sensitive Gi/Go-proteins to the norepinephrine-induced inhibition. Yohimbine but not prazosin nor propranolol antagonized the norepinephrine-induced inhibition, suggesting the involvement of alpha 2-adrenoceptor in norepinephrine-induced inhibition of the high voltage-activated calcium channels. omega-Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine and omega-conotoxin-MVIIC blocked the high voltage-activated calcium channel current by 26, 9, 36 and 11% of the total current respectively, suggesting the existence of N-, P-, L- and Q-type calcium channels in the nucleus tractus solitarii neurons. The current being insensitive to these calcium channel antagonists, termed R-type calcium channel current, also existed. This residual R-type calcium channel was completely blocked by adding 200 microM CD2+. The norepinephrine significantly inhibited N- and P-type calcium channels.(ABSTRACT TRUNCATED AT 250 WORDS)