Altered properties of quantal neurotransmitter release at endplates of mice lacking P/Q-type Ca2+ channels

URBANO FJ ; PIEDRAS-RENTERÍA ES ; JUN K; SHIN H-S; UCHITEL OD; TSIEN RW

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

NATL ACAD SCIENCES

Lugar: Washington, DC. USA.; Año: 2003 vol. 100 p. 3491 - 3496

0027-8424

Transmission at the mouse neuromuscular junction normally relies on P/Q-type channels, but became jointly dependent on both N and R-type Ca channels when the P/Q-type channel alpha1A subunit was deleted. R-type channels lay close to Ca sensors for exocytosis and IK(Ca) channel activation, like the P/Q-type channels they replaced. In contrast, N-type channels were less well localized, but abundant enough to influence secretion strongly, particularly when action potentials were prolonged. Our data suggested that active zone structures may select among multiple Ca channels in the hierarchy P/Q>R>N. The alpha1A deficient neuromuscular junction displayed several other differences from wild-type: lowered quantal content but greater ability to withstand reductions in the Ca/Mg-ratio, and little or no paired-pulse facilitation, the latter findings possibly reflecting compensatory mechanisms at individual release sites. Changes in presynaptic function were also associated with a significant reduction in the size of postsynaptic acetylcholine receptor clusters.