Voltage-gated calcium channels are not involved in generation and propagation of spreading depression (SD) in the brainstem of immature rats.
Spreading depression (SD) can be elicited in the brainstem of rats younger than 13 days when excitability is enhanced by acetate superfusion [F. Richter, S. Rupprecht, A. Lehmenkühler, H.-G. Schaible, Spreading depression can be elicited in brain stem in immature but not adult rats, J. Neurophysiol. 90 (2003) 2163--2170]. To investigate whether voltage-gated calcium channels (VGCCs) modify initiation and propagation of SD in this type of tissue, we applied specific blockers to L-, T-, P/Q-, and N-type VGCCs locally or systemically. SD-related d.c. potentials and concomitant increases in extracellular potassium concentration ([K(+)](e)) were unaffected by the L- and T-type VGCC blocker flunarizine that was applied either systemically (up to 2mg/kg body weight) or by superfusion onto the brainstem (40 microM). In addition, local application of the P/Q-type VGCC blocker omega-agatoxin (1 microM) or of the N-type VGCC blocker omega-conotoxin (1 microM) to the brainstem surface did not influence SD. The results indicate that VGCCs do not modify the generation or propagation of SDs in the brainstem of the immature rat. Blockade of N-type VGCCs disturbed the normal breathing rhythm. Application of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) (250-1000 microM) that elicited SD in the immature cortex, failed to elicit SD in the immature brainstem. In summary, it is likely that K(+) initiates and propagates brainstem SDs.
Richter
Frank
F
Institute of Physiology I - Neurophysiology, Friedrich Schiller University Jena, Teichgraben 8, D-07740 Jena, Germany. frank.richter@mti.uni-jena.de
Lehmenkühler
Alfred
A
Schaible
Hans-Georg
HG
D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D015220:Calcium Channels / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects; D005444:Flunarizine / Q000008:administration & dosage*; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D005444:Flunarizine