Calcium channels involved in synaptic transmission at the mature and regenerating mouse neuromuscular junction.
1. The involvement of the different types of voltage-dependent calcium channels (VDCCs) in synaptic transmission at the mature and newly formed mammalian neuromuscular junction was studied by evaluating the effects of L-, P/Q- and N-type VDCC antagonists on transmitter release in normal and reinnervating levator auris preparations of adult mice. 2. Nerve-evoked transmitter release was blocked by omega-agatoxin IVA (omega-AgaIVA), a P/Q-type VDCC blocker, both in normal and reinnervating endplates (100 nM omega-AgaIVA caused > 90% inhibition). The N-type VDCC antagonist omega-conotoxin GVIA (omega-CgTX; 1 and 5 microM), as occurs in normal preparations, did not significantly affect this type of release during reinnervation. Nitrendipine (1-10 microM), an L-type VDCC blocker, strongly antagonized release in reinnervating muscles (approximately 40-69% blockade) and lacked any effect in normal preparations. 3. In reinnervating muscles, spontaneous release was not dependent on Ca2+ entry through either P- or L-type VDCCs. Neither 100 nM omega-AgaIVA nor 10 microM nitrendipine affected the miniature endplate potential (MEPP) frequency or amplitude. 4. At the newly formed endplates, K(+)-evoked release was dependent on Ca2+ entry through VDCCs of the P-type family (100 nM omega-AgaIVA reduced approximately 70% of the K(+)-evoked MEPP frequency). L-type VDCCs were found not to participate in this type of release (10 microM nitrendipine lacked any effect). 5. In reinnervating muscles, the L-type VDCC blocker, nitrendipine (10 microM), provoked a significant increase (approximately 25%) in the latency of the evoked endplate potential (EPP). This drug also caused an increase (approximately 0.3 ms) in the latency of the presynaptic currents. The P/Q- and Ny-type VDCC blockers did not affect the latency of the EPP. 6. These results show that at newly formed mouse neuromuscular junctions, as occurs in mature preparations, VDCCs of the P-type family play a prominent role in evoked transmitter release whereas N-type channels are not involved in this process. In addition, signal conduction and transmitter release become highly sensitive to nitrendipine during reinnervation. This suggests that L-type VDCCs may play a role in synaptic transmission at the immature mammalian neuromuscular junction.
Katz
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Instituto de Bilogía Celular y Neurociencias Profesor Eduardo de Robertis, Facultad de Medicina, Universidad de Buenos Aires, Paraguay, Argentina.
Ferro
P A
PA
Weisz
G
G
Uchitel
O D
OD
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D005071:Evoked Potentials; D008297:Male; D051379:Mice; D008978:Mollusk Venoms / Q000494:pharmacology; D009469:Neuromuscular Junction / Q000502:physiology*; D009568:Nitrendipine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D012038:Regeneration; D013111:Spider Venoms / Q000494:pharmacology; D009435:Synaptic Transmission / Q000502:physiology*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D008978:Mollusk Venoms; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D009568:Nitrendipine; D011188:Potassium